PSMB10: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
m (Bot: HTTP→HTTPS)
 
m (1 revision imported)
 
(One intermediate revision by one other user not shown)
Line 2: Line 2:
'''Proteasome subunit beta type-10''' as known as '''20S proteasome subunit beta-2i''' is a [[protein]] that in humans is encoded by the ''PSMB10'' [[gene]].<ref name="pmid8268911">{{cite journal | vauthors = Larsen F, Solheim J, Kristensen T, Kolstø AB, Prydz H | title = A tight cluster of five unrelated human genes on chromosome 16q22.1 | journal = Human Molecular Genetics | volume = 2 | issue = 10 | pages = 1589–95 | date = Oct 1993 | pmid = 8268911 | pmc =  | doi = 10.1093/hmg/2.10.1589 }}</ref>
'''Proteasome subunit beta type-10''' as known as '''20S proteasome subunit beta-2i''' is a [[protein]] that in humans is encoded by the ''PSMB10'' [[gene]].<ref name="pmid8268911">{{cite journal | vauthors = Larsen F, Solheim J, Kristensen T, Kolstø AB, Prydz H | title = A tight cluster of five unrelated human genes on chromosome 16q22.1 | journal = Human Molecular Genetics | volume = 2 | issue = 10 | pages = 1589–95 | date = Oct 1993 | pmid = 8268911 | pmc =  | doi = 10.1093/hmg/2.10.1589 }}</ref>


This protein has a major role in the immune system as part of an immunoproteasome that is primarily induced upon infection and formed by replacing constitutive beta subunits with inducible beta subunits which possess specific cleavage properties that aid in the release of peptides necessary for MHC class I antigen presentation.<ref>{{cite journal | vauthors = Kasthuri SR, Umasuthan N, Whang I, Lim BS, Jung HB, Oh MJ, Jung SJ, Yeo SY, Kim SY, Lee J | title = Molecular characterization and expressional affirmation of the beta proteasome subunit cluster in rock bream immune defense | journal = Molecular Biology Reports | volume = 41 | issue = 8 | pages = 5413–27 | date = Aug 2014 | pmid = 24867079 | doi = 10.1007/s11033-014-3413-1 }}</ref> The immunoproteasome appears to have a pivotal role in modulating NFκB signaling.<ref>{{cite journal | vauthors = Maldonado M, Kapphahn RJ, Terluk MR, Heuss ND, Yuan C, Gregerson DS, Ferrington DA | title = Immunoproteasome deficiency modifies the alternative pathway of NFκB signaling | journal = PLOS ONE | volume = 8 | issue = 2 | pages = e56187 | date = 2013 | pmid = 23457524 | pmc = 3572990 | doi = 10.1371/journal.pone.0056187 | bibcode = 2013PLoSO...856187M }}</ref>
This protein has a major role in the immune system as part of an immunoproteasome that is primarily induced upon infection and formed by replacing constitutive beta subunits with inducible beta subunits which possess specific cleavage properties that aid in the release of peptides necessary for MHC class I antigen presentation.<ref name="ReferenceD">{{cite journal | vauthors = Kasthuri SR, Umasuthan N, Whang I, Lim BS, Jung HB, Oh MJ, Jung SJ, Yeo SY, Kim SY, Lee J | title = Molecular characterization and expressional affirmation of the beta proteasome subunit cluster in rock bream immune defense | journal = Molecular Biology Reports | volume = 41 | issue = 8 | pages = 5413–27 | date = Aug 2014 | pmid = 24867079 | doi = 10.1007/s11033-014-3413-1 }}</ref> The immunoproteasome appears to have a pivotal role in modulating NFκB signaling.<ref>{{cite journal | vauthors = Maldonado M, Kapphahn RJ, Terluk MR, Heuss ND, Yuan C, Gregerson DS, Ferrington DA | title = Immunoproteasome deficiency modifies the alternative pathway of NFκB signaling | journal = PLOS ONE | volume = 8 | issue = 2 | pages = e56187 | date = 2013 | pmid = 23457524 | pmc = 3572990 | doi = 10.1371/journal.pone.0056187 | bibcode = 2013PLoSO...856187M }}</ref>


== Structure ==
== Structure ==
Line 25: Line 25:
Protein functions are supported by its tertiary structure and its interaction with associating partners. As one of 28 subunits of 20S proteasome, protein proteasome subunit beta type-2 contributes to form a proteolytic environment for substrate degradation. Evidences of the crystal structures of isolated 20S proteasome complex demonstrate that the two rings of beta subunits form a proteolytic chamber and maintain all their active sites of proteolysis within the chamber.<ref name="ReferenceB"/> Concomitantly, the rings of alpha subunits form the entrance for substrates entering the proteolytic chamber. In an inactivated 20S proteasome complex, the gate into the internal proteolytic chamber are guarded by the [[N-terminal]] tails of specific alpha-subunit. This unique structure design prevents random encounter between proteolytic active sites and protein substrate, which makes protein degradation a well-regulated process.<ref>{{cite journal | vauthors = Groll M, Ditzel L, Löwe J, Stock D, Bochtler M, Bartunik HD, Huber R | title = Structure of 20S proteasome from yeast at 2.4 A resolution | journal = Nature | volume = 386 | issue = 6624 | pages = 463–71 | date = Apr 1997 | pmid = 9087403 | doi = 10.1038/386463a0 | bibcode = 1997Natur.386..463G }}</ref><ref name="ReferenceA">{{cite journal | vauthors = Groll M, Bajorek M, Köhler A, Moroder L, Rubin DM, Huber R, Glickman MH, Finley D | title = A gated channel into the proteasome core particle | journal = Nature Structural Biology | volume = 7 | issue = 11 | pages = 1062–7 | date = Nov 2000 | pmid = 11062564 | doi = 10.1038/80992 }}</ref> 20S proteasome complex, by itself, is usually functionally inactive. The proteolytic capacity of 20S core particle (CP) can be activated when CP associates with one or two regulatory particles (RP) on one or both side of alpha rings. These regulatory particles include 19S proteasome complexes, 11S proteasome complex, etc. Following the CP-RP association, the confirmation of certain alpha subunits will change and consequently cause the opening of substrate entrance gate. Besides RPs, the 20S proteasomes can also be effectively activated by other mild chemical treatments, such as exposure to low levels of sodium dodecylsulfate (SDS) or NP-14.<ref name="ReferenceA"/><ref>{{cite journal | vauthors = Zong C, Gomes AV, Drews O, Li X, Young GW, Berhane B, Qiao X, French SW, Bardag-Gorce F, Ping P | title = Regulation of murine cardiac 20S proteasomes: role of associating partners | journal = Circulation Research | volume = 99 | issue = 4 | pages = 372–80 | date = Aug 2006 | pmid = 16857963 | doi = 10.1161/01.RES.0000237389.40000.02 }}</ref>
Protein functions are supported by its tertiary structure and its interaction with associating partners. As one of 28 subunits of 20S proteasome, protein proteasome subunit beta type-2 contributes to form a proteolytic environment for substrate degradation. Evidences of the crystal structures of isolated 20S proteasome complex demonstrate that the two rings of beta subunits form a proteolytic chamber and maintain all their active sites of proteolysis within the chamber.<ref name="ReferenceB"/> Concomitantly, the rings of alpha subunits form the entrance for substrates entering the proteolytic chamber. In an inactivated 20S proteasome complex, the gate into the internal proteolytic chamber are guarded by the [[N-terminal]] tails of specific alpha-subunit. This unique structure design prevents random encounter between proteolytic active sites and protein substrate, which makes protein degradation a well-regulated process.<ref>{{cite journal | vauthors = Groll M, Ditzel L, Löwe J, Stock D, Bochtler M, Bartunik HD, Huber R | title = Structure of 20S proteasome from yeast at 2.4 A resolution | journal = Nature | volume = 386 | issue = 6624 | pages = 463–71 | date = Apr 1997 | pmid = 9087403 | doi = 10.1038/386463a0 | bibcode = 1997Natur.386..463G }}</ref><ref name="ReferenceA">{{cite journal | vauthors = Groll M, Bajorek M, Köhler A, Moroder L, Rubin DM, Huber R, Glickman MH, Finley D | title = A gated channel into the proteasome core particle | journal = Nature Structural Biology | volume = 7 | issue = 11 | pages = 1062–7 | date = Nov 2000 | pmid = 11062564 | doi = 10.1038/80992 }}</ref> 20S proteasome complex, by itself, is usually functionally inactive. The proteolytic capacity of 20S core particle (CP) can be activated when CP associates with one or two regulatory particles (RP) on one or both side of alpha rings. These regulatory particles include 19S proteasome complexes, 11S proteasome complex, etc. Following the CP-RP association, the confirmation of certain alpha subunits will change and consequently cause the opening of substrate entrance gate. Besides RPs, the 20S proteasomes can also be effectively activated by other mild chemical treatments, such as exposure to low levels of sodium dodecylsulfate (SDS) or NP-14.<ref name="ReferenceA"/><ref>{{cite journal | vauthors = Zong C, Gomes AV, Drews O, Li X, Young GW, Berhane B, Qiao X, French SW, Bardag-Gorce F, Ping P | title = Regulation of murine cardiac 20S proteasomes: role of associating partners | journal = Circulation Research | volume = 99 | issue = 4 | pages = 372–80 | date = Aug 2006 | pmid = 16857963 | doi = 10.1161/01.RES.0000237389.40000.02 }}</ref>


The 20S proteasome subunit beta-2i (systematic nomenclature) is originally expressed as a precursor with 273 amino acids. The fragment of 39 amino acids at peptide N-terminal is essential for proper protein folding and subsequent complex assembly. At the end-stage of complex assembly, the N-terminal fragment of beta2i subunit is cleaved, forming the mature beta2i subunit of 20S complex.<ref>{{cite journal | vauthors = Yang Y, Früh K, Ahn K, Peterson PA | title = In vivo assembly of the proteasomal complexes, implications for antigen processing | journal = The Journal of Biological Chemistry | volume = 270 | issue = 46 | pages = 27687–94 | date = Nov 1995 | pmid = 7499235 | doi=10.1074/jbc.270.46.27687}}</ref>  During the basal assembly,  and [[Proteolysis|proteolytic processing]] is required to generate a mature subunit. The subunit beta5i only presents in the immunoproteasome and is replaced by subunit beta5(proteasome beta 5 subunit) in constitutive 20S proteasome complex. This protein has an important function in the immune system as part of an immunoproteasome which possess specific cleavage properties that aid in the release of peptides necessary for MHC class I antigen presentation.<ref>{{cite journal | vauthors = Kasthuri SR, Umasuthan N, Whang I, Lim BS, Jung HB, Oh MJ, Jung SJ, Yeo SY, Kim SY, Lee J | title = Molecular characterization and expressional affirmation of the beta proteasome subunit cluster in rock bream immune defense | journal = Molecular Biology Reports | volume = 41 | issue = 8 | pages = 5413–27 | date = Aug 2014 | pmid = 24867079 | doi = 10.1007/s11033-014-3413-1 }}</ref>
The 20S proteasome subunit beta-2i (systematic nomenclature) is originally expressed as a precursor with 273 amino acids. The fragment of 39 amino acids at peptide N-terminal is essential for proper protein folding and subsequent complex assembly. At the end-stage of complex assembly, the N-terminal fragment of beta2i subunit is cleaved, forming the mature beta2i subunit of 20S complex.<ref>{{cite journal | vauthors = Yang Y, Früh K, Ahn K, Peterson PA | title = In vivo assembly of the proteasomal complexes, implications for antigen processing | journal = The Journal of Biological Chemistry | volume = 270 | issue = 46 | pages = 27687–94 | date = Nov 1995 | pmid = 7499235 | doi=10.1074/jbc.270.46.27687}}</ref>  During the basal assembly,  and [[Proteolysis|proteolytic processing]] is required to generate a mature subunit. The subunit beta5i only presents in the immunoproteasome and is replaced by subunit beta5(proteasome beta 5 subunit) in constitutive 20S proteasome complex. This protein has an important function in the immune system as part of an immunoproteasome which possess specific cleavage properties that aid in the release of peptides necessary for MHC class I antigen presentation.<ref name="ReferenceD"/>


== Clinical significance ==
== Clinical significance ==
Line 33: Line 33:
The proteasomes form a pivotal component for the [[proteasome|Ubiquitin-Proteasome System (UPS)]] <ref>{{cite journal | vauthors = Kleiger G, Mayor T | title = Perilous journey: a tour of the ubiquitin-proteasome system | journal = Trends in Cell Biology | volume = 24 | issue = 6 | pages = 352–9 | date = Jun 2014 | pmid = 24457024 | pmc = 4037451 | doi = 10.1016/j.tcb.2013.12.003 }}</ref> and corresponding cellular Protein Quality Control (PQC). Protein [[ubiquitination]] and subsequent [[proteolysis]] and degradation by the proteasome are important mechanisms in the regulation of the [[cell cycle]], [[cell growth]] and differentiation, gene transcription, signal transduction and [[apoptosis]].<ref>{{cite journal | vauthors = Goldberg AL, Stein R, Adams J | title = New insights into proteasome function: from archaebacteria to drug development | journal = Chemistry & Biology | volume = 2 | issue = 8 | pages = 503–8 | date = Aug 1995 | pmid = 9383453 | doi=10.1016/1074-5521(95)90182-5}}</ref> Subsequently, a compromised proteasome complex assembly and function lead to reduced proteolytic activities and the accumulation of damaged or misfolded protein species. Such protein accumulation may contribute to the pathogenesis and phenotypic characteristics in neurodegenerative diseases,<ref>{{cite journal | vauthors = Sulistio YA, Heese K | title = The Ubiquitin-Proteasome System and Molecular Chaperone Deregulation in Alzheimer's Disease | journal = Molecular Neurobiology | date = Jan 2015 | pmid = 25561438 | doi = 10.1007/s12035-014-9063-4 | volume=53 | pages=905–31}}</ref><ref>{{cite journal | vauthors = Ortega Z, Lucas JJ | title = Ubiquitin-proteasome system involvement in Huntington's disease | journal = Frontiers in Molecular Neuroscience | volume = 7 | pages = 77 | date = 2014 | pmid = 25324717 | pmc = 4179678 | doi = 10.3389/fnmol.2014.00077 }}</ref> cardiovascular diseases,<ref>{{cite journal | vauthors = Sandri M, Robbins J | title = Proteotoxicity: an underappreciated pathology in cardiac disease | journal = Journal of Molecular and Cellular Cardiology | volume = 71 | pages = 3–10 | date = Jun 2014 | pmid = 24380730 | pmc = 4011959 | doi = 10.1016/j.yjmcc.2013.12.015 }}</ref><ref>{{cite journal | vauthors = Drews O, Taegtmeyer H | title = Targeting the ubiquitin-proteasome system in heart disease: the basis for new therapeutic strategies | journal = Antioxidants & Redox Signaling | volume = 21 | issue = 17 | pages = 2322–43 | date = Dec 2014 | pmid = 25133688 | pmc = 4241867 | doi = 10.1089/ars.2013.5823 }}</ref><ref>{{cite journal | vauthors = Wang ZV, Hill JA | title = Protein quality control and metabolism: bidirectional control in the heart | journal = Cell Metabolism | volume = 21 | issue = 2 | pages = 215–26 | date = Feb 2015 | pmid = 25651176 | pmc = 4317573 | doi = 10.1016/j.cmet.2015.01.016 }}</ref> inflammatory responses and autoimmune diseases,<ref name="Karin M 2000">{{cite journal | vauthors = Karin M, Delhase M | title = The I kappa B kinase (IKK) and NF-kappa B: key elements of proinflammatory signalling | journal = Seminars in Immunology | volume = 12 | issue = 1 | pages = 85–98 | date = Feb 2000 | pmid = 10723801 | doi = 10.1006/smim.2000.0210 }}</ref>  and systemic DNA damage responses leading to [[malignancies]].<ref>{{cite journal | vauthors = Ermolaeva MA, Dakhovnik A, Schumacher B | title = Quality control mechanisms in cellular and systemic DNA damage responses | journal = Ageing Research Reviews | volume = 23 | issue = Pt A | pages = 3–11 | date = Jan 2015 | pmid = 25560147 | doi = 10.1016/j.arr.2014.12.009 | pmc=4886828}}</ref>
The proteasomes form a pivotal component for the [[proteasome|Ubiquitin-Proteasome System (UPS)]] <ref>{{cite journal | vauthors = Kleiger G, Mayor T | title = Perilous journey: a tour of the ubiquitin-proteasome system | journal = Trends in Cell Biology | volume = 24 | issue = 6 | pages = 352–9 | date = Jun 2014 | pmid = 24457024 | pmc = 4037451 | doi = 10.1016/j.tcb.2013.12.003 }}</ref> and corresponding cellular Protein Quality Control (PQC). Protein [[ubiquitination]] and subsequent [[proteolysis]] and degradation by the proteasome are important mechanisms in the regulation of the [[cell cycle]], [[cell growth]] and differentiation, gene transcription, signal transduction and [[apoptosis]].<ref>{{cite journal | vauthors = Goldberg AL, Stein R, Adams J | title = New insights into proteasome function: from archaebacteria to drug development | journal = Chemistry & Biology | volume = 2 | issue = 8 | pages = 503–8 | date = Aug 1995 | pmid = 9383453 | doi=10.1016/1074-5521(95)90182-5}}</ref> Subsequently, a compromised proteasome complex assembly and function lead to reduced proteolytic activities and the accumulation of damaged or misfolded protein species. Such protein accumulation may contribute to the pathogenesis and phenotypic characteristics in neurodegenerative diseases,<ref>{{cite journal | vauthors = Sulistio YA, Heese K | title = The Ubiquitin-Proteasome System and Molecular Chaperone Deregulation in Alzheimer's Disease | journal = Molecular Neurobiology | date = Jan 2015 | pmid = 25561438 | doi = 10.1007/s12035-014-9063-4 | volume=53 | pages=905–31}}</ref><ref>{{cite journal | vauthors = Ortega Z, Lucas JJ | title = Ubiquitin-proteasome system involvement in Huntington's disease | journal = Frontiers in Molecular Neuroscience | volume = 7 | pages = 77 | date = 2014 | pmid = 25324717 | pmc = 4179678 | doi = 10.3389/fnmol.2014.00077 }}</ref> cardiovascular diseases,<ref>{{cite journal | vauthors = Sandri M, Robbins J | title = Proteotoxicity: an underappreciated pathology in cardiac disease | journal = Journal of Molecular and Cellular Cardiology | volume = 71 | pages = 3–10 | date = Jun 2014 | pmid = 24380730 | pmc = 4011959 | doi = 10.1016/j.yjmcc.2013.12.015 }}</ref><ref>{{cite journal | vauthors = Drews O, Taegtmeyer H | title = Targeting the ubiquitin-proteasome system in heart disease: the basis for new therapeutic strategies | journal = Antioxidants & Redox Signaling | volume = 21 | issue = 17 | pages = 2322–43 | date = Dec 2014 | pmid = 25133688 | pmc = 4241867 | doi = 10.1089/ars.2013.5823 }}</ref><ref>{{cite journal | vauthors = Wang ZV, Hill JA | title = Protein quality control and metabolism: bidirectional control in the heart | journal = Cell Metabolism | volume = 21 | issue = 2 | pages = 215–26 | date = Feb 2015 | pmid = 25651176 | pmc = 4317573 | doi = 10.1016/j.cmet.2015.01.016 }}</ref> inflammatory responses and autoimmune diseases,<ref name="Karin M 2000">{{cite journal | vauthors = Karin M, Delhase M | title = The I kappa B kinase (IKK) and NF-kappa B: key elements of proinflammatory signalling | journal = Seminars in Immunology | volume = 12 | issue = 1 | pages = 85–98 | date = Feb 2000 | pmid = 10723801 | doi = 10.1006/smim.2000.0210 }}</ref>  and systemic DNA damage responses leading to [[malignancies]].<ref>{{cite journal | vauthors = Ermolaeva MA, Dakhovnik A, Schumacher B | title = Quality control mechanisms in cellular and systemic DNA damage responses | journal = Ageing Research Reviews | volume = 23 | issue = Pt A | pages = 3–11 | date = Jan 2015 | pmid = 25560147 | doi = 10.1016/j.arr.2014.12.009 | pmc=4886828}}</ref>


Several experimental and clinical studies have indicated that aberrations and deregulations of the UPS contribute to the pathogenesis of several neurodegenerative and myodegenerative disorders, including [[Alzheimer's disease]],<ref>{{cite journal | vauthors = Checler F, da Costa CA, Ancolio K, Chevallier N, Lopez-Perez E, Marambaud P | title = Role of the proteasome in Alzheimer's disease | journal = Biochimica et Biophysica Acta | volume = 1502 | issue = 1 | pages = 133–8 | date = Jul 2000 | pmid = 10899438 | doi=10.1016/s0925-4439(00)00039-9}}</ref> [[Parkinson's disease]]<ref name="ReferenceC">{{cite journal | vauthors = Chung KK, Dawson VL, Dawson TM | title = The role of the ubiquitin-proteasomal pathway in Parkinson's disease and other neurodegenerative disorders | journal = Trends in Neurosciences | volume = 24 | issue = 11 Suppl | pages = S7–14 | date = Nov 2001 | pmid = 11881748 | doi=10.1016/s0166-2236(00)01998-6}}</ref> and [[Pick's disease]],<ref name="IkedaAkiyama2002">{{cite journal | vauthors = Ikeda K, Akiyama H, Arai T, Ueno H, Tsuchiya K, Kosaka K | title = Morphometrical reappraisal of motor neuron system of Pick's disease and amyotrophic lateral sclerosis with dementia | journal = Acta Neuropathologica | volume = 104 | issue = 1 | pages = 21–8 | date = Jul 2002 | pmid = 12070660 | doi = 10.1007/s00401-001-0513-5 }}</ref> [[Amyotrophic lateral sclerosis]] ([[ALS]]),<ref name="IkedaAkiyama2002"/> [[Huntington's disease]],<ref name="ReferenceC"/> [[Creutzfeldt–Jakob disease]],<ref>{{cite journal | vauthors = Manaka H, Kato T, Kurita K, Katagiri T, Shikama Y, Kujirai K, Kawanami T, Suzuki Y, Nihei K, Sasaki H | title = Marked increase in cerebrospinal fluid ubiquitin in Creutzfeldt–Jakob disease | journal = Neuroscience Letters | volume = 139 | issue = 1 | pages = 47–9 | date = May 1992 | pmid = 1328965 | doi=10.1016/0304-3940(92)90854-z}}</ref> and motor neuron diseases, polyglutamine (PolyQ) diseases, [[Muscular dystrophies]]<ref>{{cite journal | vauthors = Mathews KD, Moore SA | title = Limb-girdle muscular dystrophy | journal = Current Neurology and Neuroscience Reports | volume = 3 | issue = 1 | pages = 78–85 | date = Jan 2003 | pmid = 12507416 | doi=10.1007/s11910-003-0042-9}}</ref> and several rare forms of neurodegenerative diseases associated with [[dementia]].<ref>{{cite journal | vauthors = Mayer RJ | title = From neurodegeneration to neurohomeostasis: the role of ubiquitin | journal = Drug News & Perspectives | volume = 16 | issue = 2 | pages = 103–8 | date = Mar 2003 | pmid = 12792671 | doi=10.1358/dnp.2003.16.2.829327}}</ref> As part of the [[proteasome|Ubiquitin-Proteasome System (UPS)]], the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac [[Ischemic]] injury,<ref>{{cite journal | vauthors = Calise J, Powell SR | title = The ubiquitin proteasome system and myocardial ischemia | journal = American Journal of Physiology. Heart and Circulatory Physiology | volume = 304 | issue = 3 | pages = H337–49 | date = Feb 2013 | pmid = 23220331 | pmc = 3774499 | doi = 10.1152/ajpheart.00604.2012 }}</ref> [[ventricular hypertrophy]]<ref>{{cite journal | vauthors = Predmore JM, Wang P, Davis F, Bartolone S, Westfall MV, Dyke DB, Pagani F, Powell SR, Day SM | title = Ubiquitin proteasome dysfunction in human hypertrophic and dilated cardiomyopathies | journal = Circulation | volume = 121 | issue = 8 | pages = 997–1004 | date = Mar 2010 | pmid = 20159828 | pmc = 2857348 | doi = 10.1161/CIRCULATIONAHA.109.904557 }}</ref> and [[Heart failure]].<ref>{{cite journal | vauthors = Powell SR | title = The ubiquitin-proteasome system in cardiac physiology and pathology | journal = American Journal of Physiology. Heart and Circulatory Physiology | volume = 291 | issue = 1 | pages = H1–H19 | date = Jul 2006 | pmid = 16501026 | doi = 10.1152/ajpheart.00062.2006 }}</ref> Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of [[transcription factors]], such as [[p53]], [[c-Jun]], [[c-Fos]], [[NF-κB]], [[c-Myc]], HIF-1α, MATα2, [[STAT3]], sterol-regulated element-binding proteins and [[androgen receptors]] are all controlled by the UPS and thus involved in the development of various malignancies.<ref>{{cite journal | vauthors = Adams J | title = Potential for proteasome inhibition in the treatment of cancer | journal = Drug Discovery Today | volume = 8 | issue = 7 | pages = 307–15 | date = Apr 2003 | pmid = 12654543 | doi=10.1016/s1359-6446(03)02647-3}}</ref> Moreover, the UPS regulates the degradation of tumor suppressor gene products such as [[adenomatous polyposis coli]] ([[adenomatous polyposis coli|APC]]) in colorectal cancer, [[retinoblastoma]] (Rb). and [[von Hippel-Lindau tumor suppressor]] (VHL), as well as a number of [[proto-oncogenes]] ([[Raf kinase|Raf]], [[Myc]], [[MYB (gene)|Myb]], [[NF-κB|Rel]], [[Src (gene)|Src]], [[MOS (gene)|Mos]], [[Abl (gene)|Abl]]). The UPS is also involved in the regulation of inflammatory responses. This activity is usually attributed to the role of proteasomes in the activation of NF-κB which further regulates the expression of pro inflammatory [[cytokines]] such as [[TNF-α]], IL-β, [[Interleukin 8|IL-8]], [[adhesion molecules]] ([[ICAM-1]], [[VCAM-1]], P selectine) and [[prostaglandins]] and [[nitric oxide]] (NO).<ref name="Karin M 2000"/> Additionally, the UPS also plays a role in inflammatory responses as regulators of leukocyte proliferation, mainly through proteolysis of cyclines and the degradation of [[Cyclin-dependent kinase|CDK]] inhibitors.<ref>{{cite journal | vauthors = Ben-Neriah Y | title = Regulatory functions of ubiquitination in the immune system | journal = Nature Immunology | volume = 3 | issue = 1 | pages = 20–6 | date = Jan 2002 | pmid = 11753406 | doi = 10.1038/ni0102-20 }}</ref> Lastly, [[autoimmune disease]] patients with [[Systemic lupus erythematosus|SLE]], [[Sjogren's syndrome]] and [[rheumatoid arthritis]] (RA) predominantly exhibit circulating proteasomes which can be applied as clinical biomarkers.<ref>{{cite journal | vauthors = Egerer K, Kuckelkorn U, Rudolph PE, Rückert JC, Dörner T, Burmester GR, Kloetzel PM, Feist E | title = Circulating proteasomes are markers of cell damage and immunologic activity in autoimmune diseases | journal = The Journal of Rheumatology | volume = 29 | issue = 10 | pages = 2045–52 | date = Oct 2002 | pmid = 12375310 }}</ref>
Several experimental and clinical studies have indicated that aberrations and deregulations of the UPS contribute to the pathogenesis of several neurodegenerative and myodegenerative disorders, including [[Alzheimer's disease]],<ref>{{cite journal | vauthors = Checler F, da Costa CA, Ancolio K, Chevallier N, Lopez-Perez E, Marambaud P | title = Role of the proteasome in Alzheimer's disease | journal = Biochimica et Biophysica Acta | volume = 1502 | issue = 1 | pages = 133–8 | date = Jul 2000 | pmid = 10899438 | doi=10.1016/s0925-4439(00)00039-9}}</ref> [[Parkinson's disease]]<ref name="ReferenceC">{{cite journal | vauthors = Chung KK, Dawson VL, Dawson TM | title = The role of the ubiquitin-proteasomal pathway in Parkinson's disease and other neurodegenerative disorders | journal = Trends in Neurosciences | volume = 24 | issue = 11 Suppl | pages = S7–14 | date = Nov 2001 | pmid = 11881748 | doi=10.1016/s0166-2236(00)01998-6}}</ref> and [[Pick's disease]],<ref name="IkedaAkiyama2002">{{cite journal | vauthors = Ikeda K, Akiyama H, Arai T, Ueno H, Tsuchiya K, Kosaka K | title = Morphometrical reappraisal of motor neuron system of Pick's disease and amyotrophic lateral sclerosis with dementia | journal = Acta Neuropathologica | volume = 104 | issue = 1 | pages = 21–8 | date = Jul 2002 | pmid = 12070660 | doi = 10.1007/s00401-001-0513-5 }}</ref> [[Amyotrophic lateral sclerosis]] ([[ALS]]),<ref name="IkedaAkiyama2002"/> [[Huntington's disease]],<ref name="ReferenceC"/> [[Creutzfeldt–Jakob disease]],<ref>{{cite journal | vauthors = Manaka H, Kato T, Kurita K, Katagiri T, Shikama Y, Kujirai K, Kawanami T, Suzuki Y, Nihei K, Sasaki H | title = Marked increase in cerebrospinal fluid ubiquitin in Creutzfeldt–Jakob disease | journal = Neuroscience Letters | volume = 139 | issue = 1 | pages = 47–9 | date = May 1992 | pmid = 1328965 | doi=10.1016/0304-3940(92)90854-z}}</ref> and motor neuron diseases, polyglutamine (PolyQ) diseases, [[Muscular dystrophies]]<ref>{{cite journal | vauthors = Mathews KD, Moore SA | title = Limb-girdle muscular dystrophy | journal = Current Neurology and Neuroscience Reports | volume = 3 | issue = 1 | pages = 78–85 | date = Jan 2003 | pmid = 12507416 | doi=10.1007/s11910-003-0042-9}}</ref> and several rare forms of neurodegenerative diseases associated with [[dementia]].<ref>{{cite journal | vauthors = Mayer RJ | title = From neurodegeneration to neurohomeostasis: the role of ubiquitin | journal = Drug News & Perspectives | volume = 16 | issue = 2 | pages = 103–8 | date = Mar 2003 | pmid = 12792671 | doi=10.1358/dnp.2003.16.2.829327}}</ref> As part of the [[proteasome|Ubiquitin-Proteasome System (UPS)]], the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac [[Ischemic]] injury,<ref>{{cite journal | vauthors = Calise J, Powell SR | title = The ubiquitin proteasome system and myocardial ischemia | journal = American Journal of Physiology. Heart and Circulatory Physiology | volume = 304 | issue = 3 | pages = H337–49 | date = Feb 2013 | pmid = 23220331 | pmc = 3774499 | doi = 10.1152/ajpheart.00604.2012 }}</ref> [[ventricular hypertrophy]]<ref>{{cite journal | vauthors = Predmore JM, Wang P, Davis F, Bartolone S, Westfall MV, Dyke DB, Pagani F, Powell SR, Day SM | title = Ubiquitin proteasome dysfunction in human hypertrophic and dilated cardiomyopathies | journal = Circulation | volume = 121 | issue = 8 | pages = 997–1004 | date = Mar 2010 | pmid = 20159828 | pmc = 2857348 | doi = 10.1161/CIRCULATIONAHA.109.904557 }}</ref> and [[Heart failure]].<ref>{{cite journal | vauthors = Powell SR | title = The ubiquitin-proteasome system in cardiac physiology and pathology | journal = American Journal of Physiology. Heart and Circulatory Physiology | volume = 291 | issue = 1 | pages = H1–H19 | date = Jul 2006 | pmid = 16501026 | doi = 10.1152/ajpheart.00062.2006 }}</ref> Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of [[transcription factors]], such as [[p53]], [[c-Jun]], [[c-Fos]], [[NF-κB]], [[c-Myc]], HIF-1α, MATα2, [[STAT3]], sterol-regulated element-binding proteins and [[androgen receptors]] are all controlled by the UPS and thus involved in the development of various malignancies.<ref>{{cite journal | vauthors = Adams J | title = Potential for proteasome inhibition in the treatment of cancer | journal = Drug Discovery Today | volume = 8 | issue = 7 | pages = 307–15 | date = Apr 2003 | pmid = 12654543 | doi=10.1016/s1359-6446(03)02647-3}}</ref> Moreover, the UPS regulates the degradation of tumor suppressor gene products such as [[adenomatous polyposis coli]] ([[adenomatous polyposis coli|APC]]) in colorectal cancer, [[retinoblastoma]] (Rb). and [[von Hippel-Lindau tumor suppressor]] (VHL), as well as a number of [[proto-oncogenes]] ([[Raf kinase|Raf]], [[Myc]], [[MYB (gene)|Myb]], [[NF-κB|Rel]], [[Src (gene)|Src]], [[MOS (gene)|Mos]], [[Abl (gene)|Abl]]). The UPS is also involved in the regulation of inflammatory responses. This activity is usually attributed to the role of proteasomes in the activation of NF-κB which further regulates the expression of pro inflammatory [[cytokines]] such as [[TNF-α]], IL-β, [[Interleukin 8|IL-8]], [[adhesion molecules]] ([[ICAM-1]], [[VCAM-1]], [[P-selectin]]) and [[prostaglandins]] and [[nitric oxide]] (NO).<ref name="Karin M 2000"/> Additionally, the UPS also plays a role in inflammatory responses as regulators of leukocyte proliferation, mainly through proteolysis of cyclines and the degradation of [[Cyclin-dependent kinase|CDK]] inhibitors.<ref>{{cite journal | vauthors = Ben-Neriah Y | title = Regulatory functions of ubiquitination in the immune system | journal = Nature Immunology | volume = 3 | issue = 1 | pages = 20–6 | date = Jan 2002 | pmid = 11753406 | doi = 10.1038/ni0102-20 }}</ref> Lastly, [[autoimmune disease]] patients with [[Systemic lupus erythematosus|SLE]], [[Sjogren's syndrome]] and [[rheumatoid arthritis]] (RA) predominantly exhibit circulating proteasomes which can be applied as clinical biomarkers.<ref>{{cite journal | vauthors = Egerer K, Kuckelkorn U, Rudolph PE, Rückert JC, Dörner T, Burmester GR, Kloetzel PM, Feist E | title = Circulating proteasomes are markers of cell damage and immunologic activity in autoimmune diseases | journal = The Journal of Rheumatology | volume = 29 | issue = 10 | pages = 2045–52 | date = Oct 2002 | pmid = 12375310 }}</ref>


During the antigen processing for the major histocompatibility complex (MHC) class-I,  the proteasome is the major degradation machinery that degrades the antigen and present the resulting peptides to cytotoxic T lymphocytes.<ref>{{cite journal | vauthors = Basler M, Lauer C, Beck U, Groettrup M | title = The proteasome inhibitor bortezomib enhances the susceptibility to viral infection | journal = Journal of Immunology | volume = 183 | issue = 10 | pages = 6145–50 | date = Nov 2009 | pmid = 19841190 | doi = 10.4049/jimmunol.0901596 }}</ref><ref>{{cite journal | vauthors = Rock KL, Gramm C, Rothstein L, Clark K, Stein R, Dick L, Hwang D, Goldberg AL | title = Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules | journal = Cell | volume = 78 | issue = 5 | pages = 761–71 | date = Sep 1994 | pmid = 8087844 | doi=10.1016/s0092-8674(94)90462-6}}</ref> The immunoproteasome has been considered playing a critical role in improving the quality and quantity of generated class-I ligands.
During the antigen processing for the major histocompatibility complex (MHC) class-I,  the proteasome is the major degradation machinery that degrades the antigen and present the resulting peptides to cytotoxic T lymphocytes.<ref>{{cite journal | vauthors = Basler M, Lauer C, Beck U, Groettrup M | title = The proteasome inhibitor bortezomib enhances the susceptibility to viral infection | journal = Journal of Immunology | volume = 183 | issue = 10 | pages = 6145–50 | date = Nov 2009 | pmid = 19841190 | doi = 10.4049/jimmunol.0901596 }}</ref><ref>{{cite journal | vauthors = Rock KL, Gramm C, Rothstein L, Clark K, Stein R, Dick L, Hwang D, Goldberg AL | title = Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules | journal = Cell | volume = 78 | issue = 5 | pages = 761–71 | date = Sep 1994 | pmid = 8087844 | doi=10.1016/s0092-8674(94)90462-6}}</ref> The immunoproteasome has been considered playing a critical role in improving the quality and quantity of generated class-I ligands.

Latest revision as of 09:15, 10 January 2019

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

n/a

n/a

Ensembl

n/a

n/a

UniProt

n/a

n/a

RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Proteasome subunit beta type-10 as known as 20S proteasome subunit beta-2i is a protein that in humans is encoded by the PSMB10 gene.[1]

This protein has a major role in the immune system as part of an immunoproteasome that is primarily induced upon infection and formed by replacing constitutive beta subunits with inducible beta subunits which possess specific cleavage properties that aid in the release of peptides necessary for MHC class I antigen presentation.[2] The immunoproteasome appears to have a pivotal role in modulating NFκB signaling.[3]

Structure

Gene

This gene PSMB10 encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit. Proteolytic processing is required to generate a mature subunit. Expression of this gene is induced by gamma interferon, and this gene product replaces catalytic subunit beta2 (proteasome subunit beta type-7) in the immunoproteasome.[4] The human PSMB10 gene has 8 exons and locates at chromosome band 16q22.1.

Protein structure

The human protein proteasome subunit beta type-8 is 25 kDa in size and composed of 234 amino acids. The calculated theoretical pI of this protein is 6.07.

Complex assembly

Proteasome subunit beta type-10 is one of the 17 essential subunits (alpha subunits 1-7, constitutive beta subunits 1-7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex. In particular, proteasome subunit beta-2i, along with other beta subunits, assemble into two heptameric rings and subsequently a proteolytic chamber for substrate degradation. This protein contains "Trypsin-like" activity and is capable of cleaving after basic residues of peptide.[5] The eukaryotic proteasome recognized degradable proteins, including damaged proteins for protein quality control purpose or key regulatory protein components for dynamic biological processes. The constitutive subunit beta1, beta2, and beta 5 (systematic nomenclature) can be replaced by their inducible counterparts beta1i, 2i, and 5i when cells are under the treatment of interferon-γ. The resulting proteasome complex becomes the so-called immunoproteasome. An essential function of the modified proteasome complex, the immunoproteasome, is the processing of numerous MHC class-I restricted T cell epitopes.[6]

The proteasome is a multicatalytic proteinase complex with a highly ordered 20S core structure. This barrel-shaped core structure is composed of 4 axially stacked rings of 28 non-identical subunits: the two end rings are each formed by 7 alpha subunits, and the two central rings are each formed by 7 beta subunits. Three beta subunits (beta1, beta2, beta5) each contains a proteolytic active site and has distinct substrate preferences. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway.[7][8]

Function

Protein functions are supported by its tertiary structure and its interaction with associating partners. As one of 28 subunits of 20S proteasome, protein proteasome subunit beta type-2 contributes to form a proteolytic environment for substrate degradation. Evidences of the crystal structures of isolated 20S proteasome complex demonstrate that the two rings of beta subunits form a proteolytic chamber and maintain all their active sites of proteolysis within the chamber.[8] Concomitantly, the rings of alpha subunits form the entrance for substrates entering the proteolytic chamber. In an inactivated 20S proteasome complex, the gate into the internal proteolytic chamber are guarded by the N-terminal tails of specific alpha-subunit. This unique structure design prevents random encounter between proteolytic active sites and protein substrate, which makes protein degradation a well-regulated process.[9][10] 20S proteasome complex, by itself, is usually functionally inactive. The proteolytic capacity of 20S core particle (CP) can be activated when CP associates with one or two regulatory particles (RP) on one or both side of alpha rings. These regulatory particles include 19S proteasome complexes, 11S proteasome complex, etc. Following the CP-RP association, the confirmation of certain alpha subunits will change and consequently cause the opening of substrate entrance gate. Besides RPs, the 20S proteasomes can also be effectively activated by other mild chemical treatments, such as exposure to low levels of sodium dodecylsulfate (SDS) or NP-14.[10][11]

The 20S proteasome subunit beta-2i (systematic nomenclature) is originally expressed as a precursor with 273 amino acids. The fragment of 39 amino acids at peptide N-terminal is essential for proper protein folding and subsequent complex assembly. At the end-stage of complex assembly, the N-terminal fragment of beta2i subunit is cleaved, forming the mature beta2i subunit of 20S complex.[12] During the basal assembly, and proteolytic processing is required to generate a mature subunit. The subunit beta5i only presents in the immunoproteasome and is replaced by subunit beta5(proteasome beta 5 subunit) in constitutive 20S proteasome complex. This protein has an important function in the immune system as part of an immunoproteasome which possess specific cleavage properties that aid in the release of peptides necessary for MHC class I antigen presentation.[2]

Clinical significance

The Proteasome and its subunits are of clinical significance for at least two reasons: (1) a compromised complex assembly or a dysfunctional proteasome can be associated with the underlying pathophysiology of specific diseases, and (2) they can be exploited as drug targets for therapeutic interventions. More recently, more effort has been made to consider the proteasome for the development of novel diagnostic markers and strategies. An improved and comprehensive understanding of the pathophysiology of the proteasome should lead to clinical applications in the future.

The proteasomes form a pivotal component for the Ubiquitin-Proteasome System (UPS) [13] and corresponding cellular Protein Quality Control (PQC). Protein ubiquitination and subsequent proteolysis and degradation by the proteasome are important mechanisms in the regulation of the cell cycle, cell growth and differentiation, gene transcription, signal transduction and apoptosis.[14] Subsequently, a compromised proteasome complex assembly and function lead to reduced proteolytic activities and the accumulation of damaged or misfolded protein species. Such protein accumulation may contribute to the pathogenesis and phenotypic characteristics in neurodegenerative diseases,[15][16] cardiovascular diseases,[17][18][19] inflammatory responses and autoimmune diseases,[20] and systemic DNA damage responses leading to malignancies.[21]

Several experimental and clinical studies have indicated that aberrations and deregulations of the UPS contribute to the pathogenesis of several neurodegenerative and myodegenerative disorders, including Alzheimer's disease,[22] Parkinson's disease[23] and Pick's disease,[24] Amyotrophic lateral sclerosis (ALS),[24] Huntington's disease,[23] Creutzfeldt–Jakob disease,[25] and motor neuron diseases, polyglutamine (PolyQ) diseases, Muscular dystrophies[26] and several rare forms of neurodegenerative diseases associated with dementia.[27] As part of the Ubiquitin-Proteasome System (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac Ischemic injury,[28] ventricular hypertrophy[29] and Heart failure.[30] Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-Jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.[31] Moreover, the UPS regulates the degradation of tumor suppressor gene products such as adenomatous polyposis coli (APC) in colorectal cancer, retinoblastoma (Rb). and von Hippel-Lindau tumor suppressor (VHL), as well as a number of proto-oncogenes (Raf, Myc, Myb, Rel, Src, Mos, Abl). The UPS is also involved in the regulation of inflammatory responses. This activity is usually attributed to the role of proteasomes in the activation of NF-κB which further regulates the expression of pro inflammatory cytokines such as TNF-α, IL-β, IL-8, adhesion molecules (ICAM-1, VCAM-1, P-selectin) and prostaglandins and nitric oxide (NO).[20] Additionally, the UPS also plays a role in inflammatory responses as regulators of leukocyte proliferation, mainly through proteolysis of cyclines and the degradation of CDK inhibitors.[32] Lastly, autoimmune disease patients with SLE, Sjogren's syndrome and rheumatoid arthritis (RA) predominantly exhibit circulating proteasomes which can be applied as clinical biomarkers.[33]

During the antigen processing for the major histocompatibility complex (MHC) class-I, the proteasome is the major degradation machinery that degrades the antigen and present the resulting peptides to cytotoxic T lymphocytes.[34][35] The immunoproteasome has been considered playing a critical role in improving the quality and quantity of generated class-I ligands.

References

  1. ↑ Larsen F, Solheim J, Kristensen T, Kolstø AB, Prydz H (Oct 1993). "A tight cluster of five unrelated human genes on chromosome 16q22.1". Human Molecular Genetics. 2 (10): 1589–95. doi:10.1093/hmg/2.10.1589. PMID 8268911.
  2. ↑ 2.0 2.1 Kasthuri SR, Umasuthan N, Whang I, Lim BS, Jung HB, Oh MJ, Jung SJ, Yeo SY, Kim SY, Lee J (Aug 2014). "Molecular characterization and expressional affirmation of the beta proteasome subunit cluster in rock bream immune defense". Molecular Biology Reports. 41 (8): 5413–27. doi:10.1007/s11033-014-3413-1. PMID 24867079.
  3. ↑ Maldonado M, Kapphahn RJ, Terluk MR, Heuss ND, Yuan C, Gregerson DS, Ferrington DA (2013). "Immunoproteasome deficiency modifies the alternative pathway of NFκB signaling". PLOS ONE. 8 (2): e56187. Bibcode:2013PLoSO...856187M. doi:10.1371/journal.pone.0056187. PMC 3572990. PMID 23457524.
  4. ↑ "Entrez Gene: PSMB10 proteasome (prosome, macropain) subunit, beta type, 10".
  5. ↑ Coux O, Tanaka K, Goldberg AL (Nov 1996). "Structure and functions of the 20S and 26S proteasomes". Annual Review of Biochemistry. 65: 801–47. doi:10.1146/annurev.bi.65.070196.004101. PMID 8811196.
  6. ↑ Basler M, Kirk CJ, Groettrup M (Feb 2013). "The immunoproteasome in antigen processing and other immunological functions". Current Opinion in Immunology. 25 (1): 74–80. doi:10.1016/j.coi.2012.11.004. PMID 23219269.
  7. ↑ Coux O, Tanaka K, Goldberg AL (1996). "Structure and functions of the 20S and 26S proteasomes". Annual Review of Biochemistry. 65: 801–47. doi:10.1146/annurev.bi.65.070196.004101. PMID 8811196.
  8. ↑ 8.0 8.1 Tomko RJ, Hochstrasser M (2013). "Molecular architecture and assembly of the eukaryotic proteasome". Annual Review of Biochemistry. 82: 415–45. doi:10.1146/annurev-biochem-060410-150257. PMC 3827779. PMID 23495936.
  9. ↑ Groll M, Ditzel L, Löwe J, Stock D, Bochtler M, Bartunik HD, Huber R (Apr 1997). "Structure of 20S proteasome from yeast at 2.4 A resolution". Nature. 386 (6624): 463–71. Bibcode:1997Natur.386..463G. doi:10.1038/386463a0. PMID 9087403.
  10. ↑ 10.0 10.1 Groll M, Bajorek M, Köhler A, Moroder L, Rubin DM, Huber R, Glickman MH, Finley D (Nov 2000). "A gated channel into the proteasome core particle". Nature Structural Biology. 7 (11): 1062–7. doi:10.1038/80992. PMID 11062564.
  11. ↑ Zong C, Gomes AV, Drews O, Li X, Young GW, Berhane B, Qiao X, French SW, Bardag-Gorce F, Ping P (Aug 2006). "Regulation of murine cardiac 20S proteasomes: role of associating partners". Circulation Research. 99 (4): 372–80. doi:10.1161/01.RES.0000237389.40000.02. PMID 16857963.
  12. ↑ Yang Y, Früh K, Ahn K, Peterson PA (Nov 1995). "In vivo assembly of the proteasomal complexes, implications for antigen processing". The Journal of Biological Chemistry. 270 (46): 27687–94. doi:10.1074/jbc.270.46.27687. PMID 7499235.
  13. ↑ Kleiger G, Mayor T (Jun 2014). "Perilous journey: a tour of the ubiquitin-proteasome system". Trends in Cell Biology. 24 (6): 352–9. doi:10.1016/j.tcb.2013.12.003. PMC 4037451. PMID 24457024.
  14. ↑ Goldberg AL, Stein R, Adams J (Aug 1995). "New insights into proteasome function: from archaebacteria to drug development". Chemistry & Biology. 2 (8): 503–8. doi:10.1016/1074-5521(95)90182-5. PMID 9383453.
  15. ↑ Sulistio YA, Heese K (Jan 2015). "The Ubiquitin-Proteasome System and Molecular Chaperone Deregulation in Alzheimer's Disease". Molecular Neurobiology. 53: 905–31. doi:10.1007/s12035-014-9063-4. PMID 25561438.
  16. ↑ Ortega Z, Lucas JJ (2014). "Ubiquitin-proteasome system involvement in Huntington's disease". Frontiers in Molecular Neuroscience. 7: 77. doi:10.3389/fnmol.2014.00077. PMC 4179678. PMID 25324717.
  17. ↑ Sandri M, Robbins J (Jun 2014). "Proteotoxicity: an underappreciated pathology in cardiac disease". Journal of Molecular and Cellular Cardiology. 71: 3–10. doi:10.1016/j.yjmcc.2013.12.015. PMC 4011959. PMID 24380730.
  18. ↑ Drews O, Taegtmeyer H (Dec 2014). "Targeting the ubiquitin-proteasome system in heart disease: the basis for new therapeutic strategies". Antioxidants & Redox Signaling. 21 (17): 2322–43. doi:10.1089/ars.2013.5823. PMC 4241867. PMID 25133688.
  19. ↑ Wang ZV, Hill JA (Feb 2015). "Protein quality control and metabolism: bidirectional control in the heart". Cell Metabolism. 21 (2): 215–26. doi:10.1016/j.cmet.2015.01.016. PMC 4317573. PMID 25651176.
  20. ↑ 20.0 20.1 Karin M, Delhase M (Feb 2000). "The I kappa B kinase (IKK) and NF-kappa B: key elements of proinflammatory signalling". Seminars in Immunology. 12 (1): 85–98. doi:10.1006/smim.2000.0210. PMID 10723801.
  21. ↑ Ermolaeva MA, Dakhovnik A, Schumacher B (Jan 2015). "Quality control mechanisms in cellular and systemic DNA damage responses". Ageing Research Reviews. 23 (Pt A): 3–11. doi:10.1016/j.arr.2014.12.009. PMC 4886828. PMID 25560147.
  22. ↑ Checler F, da Costa CA, Ancolio K, Chevallier N, Lopez-Perez E, Marambaud P (Jul 2000). "Role of the proteasome in Alzheimer's disease". Biochimica et Biophysica Acta. 1502 (1): 133–8. doi:10.1016/s0925-4439(00)00039-9. PMID 10899438.
  23. ↑ 23.0 23.1 Chung KK, Dawson VL, Dawson TM (Nov 2001). "The role of the ubiquitin-proteasomal pathway in Parkinson's disease and other neurodegenerative disorders". Trends in Neurosciences. 24 (11 Suppl): S7–14. doi:10.1016/s0166-2236(00)01998-6. PMID 11881748.
  24. ↑ 24.0 24.1 Ikeda K, Akiyama H, Arai T, Ueno H, Tsuchiya K, Kosaka K (Jul 2002). "Morphometrical reappraisal of motor neuron system of Pick's disease and amyotrophic lateral sclerosis with dementia". Acta Neuropathologica. 104 (1): 21–8. doi:10.1007/s00401-001-0513-5. PMID 12070660.
  25. ↑ Manaka H, Kato T, Kurita K, Katagiri T, Shikama Y, Kujirai K, Kawanami T, Suzuki Y, Nihei K, Sasaki H (May 1992). "Marked increase in cerebrospinal fluid ubiquitin in Creutzfeldt–Jakob disease". Neuroscience Letters. 139 (1): 47–9. doi:10.1016/0304-3940(92)90854-z. PMID 1328965.
  26. ↑ Mathews KD, Moore SA (Jan 2003). "Limb-girdle muscular dystrophy". Current Neurology and Neuroscience Reports. 3 (1): 78–85. doi:10.1007/s11910-003-0042-9. PMID 12507416.
  27. ↑ Mayer RJ (Mar 2003). "From neurodegeneration to neurohomeostasis: the role of ubiquitin". Drug News & Perspectives. 16 (2): 103–8. doi:10.1358/dnp.2003.16.2.829327. PMID 12792671.
  28. ↑ Calise J, Powell SR (Feb 2013). "The ubiquitin proteasome system and myocardial ischemia". American Journal of Physiology. Heart and Circulatory Physiology. 304 (3): H337–49. doi:10.1152/ajpheart.00604.2012. PMC 3774499. PMID 23220331.
  29. ↑ Predmore JM, Wang P, Davis F, Bartolone S, Westfall MV, Dyke DB, Pagani F, Powell SR, Day SM (Mar 2010). "Ubiquitin proteasome dysfunction in human hypertrophic and dilated cardiomyopathies". Circulation. 121 (8): 997–1004. doi:10.1161/CIRCULATIONAHA.109.904557. PMC 2857348. PMID 20159828.
  30. ↑ Powell SR (Jul 2006). "The ubiquitin-proteasome system in cardiac physiology and pathology". American Journal of Physiology. Heart and Circulatory Physiology. 291 (1): H1–H19. doi:10.1152/ajpheart.00062.2006. PMID 16501026.
  31. ↑ Adams J (Apr 2003). "Potential for proteasome inhibition in the treatment of cancer". Drug Discovery Today. 8 (7): 307–15. doi:10.1016/s1359-6446(03)02647-3. PMID 12654543.
  32. ↑ Ben-Neriah Y (Jan 2002). "Regulatory functions of ubiquitination in the immune system". Nature Immunology. 3 (1): 20–6. doi:10.1038/ni0102-20. PMID 11753406.
  33. ↑ Egerer K, Kuckelkorn U, Rudolph PE, Rückert JC, Dörner T, Burmester GR, Kloetzel PM, Feist E (Oct 2002). "Circulating proteasomes are markers of cell damage and immunologic activity in autoimmune diseases". The Journal of Rheumatology. 29 (10): 2045–52. PMID 12375310.
  34. ↑ Basler M, Lauer C, Beck U, Groettrup M (Nov 2009). "The proteasome inhibitor bortezomib enhances the susceptibility to viral infection". Journal of Immunology. 183 (10): 6145–50. doi:10.4049/jimmunol.0901596. PMID 19841190.
  35. ↑ Rock KL, Gramm C, Rothstein L, Clark K, Stein R, Dick L, Hwang D, Goldberg AL (Sep 1994). "Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules". Cell. 78 (5): 761–71. doi:10.1016/s0092-8674(94)90462-6. PMID 8087844.

Further reading

Retrieved from "https://www.wikidoc.org/index.php?title=PSMB10&oldid=1524509"