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{{Infobox_gene}}
{{PBB_Controls
'''Prohibitin''', also known as '''PHB''', is a [[protein]] that in humans is encoded by the ''PHB'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: PHB prohibitin| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5245| accessdate = }}</ref>
| update_page = yes
The ''Phb'' gene has also been described in animals, fungi, plants, and unicellular eukaryotes. Prohibitins are divided in two classes, termed Type-I and Type-II prohibitins, based on their similarity to yeast PHB1 and PHB2, respectively. Each organism has at least one copy of each type of prohibitin gene.<ref>{{cite journal | vauthors = Van Aken O, Pecenková T, van de Cotte B, De Rycke R, Eeckhout D, Fromm H, De Jaeger G, Witters E, Beemster GT, Inzé D, Van Breusegem F | title = Mitochondrial type-I prohibitins of Arabidopsis thaliana are required for supporting proficient meristem development | journal = The Plant Journal | volume = 52 | issue = 5 | pages = 850–64 | date = Dec 2007 | pmid = 17883375 | doi = 10.1111/j.1365-313X.2007.03276.x }}</ref><ref name="pmid16796804">{{cite journal | vauthors = Mishra S, Murphy LC, Murphy LJ | title = The Prohibitins: emerging roles in diverse functions | journal = Journal of Cellular and Molecular Medicine | volume = 10 | issue = 2 | pages = 353–63 | year = 2006 | pmid = 16796804 | doi = 10.1111/j.1582-4934.2006.tb00404.x }}</ref>
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Discovery ==
{{GNF_Protein_box
Prohibitins are evolutionarily conserved genes that are ubiquitously expressed.  The human prohibitin gene, located on the [[BRCA1]] chromosome region 17q21, was originally thought to be a negative regulator of cell proliferation and a [[tumor suppressor]].  This anti-proliferative activity was later attributed to the 3' UTR of the PHB gene, and not to the actual protein. Mutations in human PHB have been linked to sporadic breast cancer. However, over-expression of PHB has been associated with a reduction in the androgen receptor activity and a reduction in PSA gene expression resulting in a decrease of androgen-dependent growth of cancerous prostate cells.<ref>{{cite web|last1=Dart|first1=D Alwyn|title=Manipulating prohibitin levels provides evidence for an in vivo role in androgen regulation of prostate tumours|pmc=2782800|publisher=Endocr Relat Cancer}}</ref>
| image =
Prohibitin is expressed as two transcripts with varying lengths of 3' untranslated region.  The longer transcript is present at higher levels in proliferating tissues and cells, suggesting that this longer 3' untranslated region may function as a trans-acting regulatory RNA.<ref name="entrez" />
| image_source =
| PDB =
| Name = Prohibitin
| HGNCid = 8912
| Symbol = PHB
| AltSymbols =;
| OMIM = 176705
| ECnumber = 
| Homologene = 1980
| MGIid = 97572
| GeneAtlas_image1 = PBB_GE_PHB_200658_s_at_tn.png
  | GeneAtlas_image2 = PBB_GE_PHB_200659_s_at_tn.png
  | Function = {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0016563 |text = transcription activator activity}} {{GNF_GO|id=GO:0016564 |text = transcription repressor activity}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005654 |text = nucleoplasm}} {{GNF_GO|id=GO:0005739 |text = mitochondrion}} {{GNF_GO|id=GO:0005743 |text = mitochondrial inner membrane}} {{GNF_GO|id=GO:0005887 |text = integral to plasma membrane}} {{GNF_GO|id=GO:0016020 |text = membrane}}
  | Process = {{GNF_GO|id=GO:0000074 |text = regulation of progression through cell cycle}} {{GNF_GO|id=GO:0006260 |text = DNA replication}} {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0008285 |text = negative regulation of cell proliferation}} {{GNF_GO|id=GO:0016481 |text = negative regulation of transcription}} {{GNF_GO|id=GO:0016575 |text = histone deacetylation}} {{GNF_GO|id=GO:0042981 |text = regulation of apoptosis}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 5245
    | Hs_Ensembl = ENSG00000167085
    | Hs_RefseqProtein = NP_002625
    | Hs_RefseqmRNA = NM_002634
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 17
    | Hs_GenLoc_start = 44836419
    | Hs_GenLoc_end = 44847241
    | Hs_Uniprot = P35232
    | Mm_EntrezGene = 18673
    | Mm_Ensembl =
    | Mm_RefseqmRNA = NM_008831
    | Mm_RefseqProtein = NP_032857
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 
    | Mm_GenLoc_start = 
    | Mm_GenLoc_end = 
    | Mm_Uniprot = 
  }}
}}
'''Prohibitin''', also known as '''PHB''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: PHB prohibitin| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5245| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{PBB_Summary
Prohibitins may have multiple functions including:
| section_title =  
| summary_text = Prohibitin is an evolutionarily conserved gene that is ubiquitously expressed.  It is thought to be a negative regulator of cell proliferation and may be a tumor suppressor.  Mutations in PHB have been linked to sporadic breast cancer.  Prohibitin is expressed as two transcripts with varying lengths of 3' untranslated region.  The longer transcript is present at higher levels in proliferating tissues and cells, suggesting that this longer 3' untranslated region may function as a trans-acting regulatory RNA.<ref name="entrez">{{cite web | title = Entrez Gene: PHB prohibitin| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5245| accessdate = }}</ref>
}}


==References==
=== Mitochondrial function and morphology ===
{{reflist|2}}
Prohibitins are assembled into a ring-like structure with 16–20 alternating Phb1 and Phb2 subunits in the inner mitochondrial membrane.<ref name="pmid15525670">{{cite journal | vauthors = Tatsuta T, Model K, Langer T | title = Formation of membrane-bound ring complexes by prohibitins in mitochondria | journal = Molecular Biology of the Cell | volume = 16 | issue = 1 | pages = 248–59 | date = Jan 2005 | pmid = 15525670 | pmc = 539169 | doi = 10.1091/mbc.E04-09-0807 }}</ref>  The precise molecular function of the PHB complex is not clear, but a role as chaperone for respiration chain proteins or as a general structuring scaffold required for optimal mitochondrial morphology and function are suspected. Recently, prohibitins have been demonstrated to be positive, rather than negative, regulators of cell proliferation in both plants and mice.
==Further reading==
 
{{refbegin | 2}}
=== Transcriptional modulation ===
{{PBB_Further_reading
Both human prohibitins have also been suggested to be localized in the nucleus and modulate [[Transcription (genetics)|transcriptional]] activity by interacting with various [[transcription factor]]s, including [[nuclear receptor]]s, either directly or indirectly. However, little evidence for nuclear targeting and transcription factor-binding of prohibitins has been found in other organism (yeast, plants, C. elegans, etc.), indicating that this may be a specific function in mammalian cells.<ref name="pmid10359819">{{cite journal | vauthors = Montano MM, Ekena K, Delage-Mourroux R, Chang W, Martini P, Katzenellenbogen BS | title = An estrogen receptor-selective coregulator that potentiates the effectiveness of antiestrogens and represses the activity of estrogens | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 12 | pages = 6947–52 | date = Jun 1999 | pmid = 10359819 | pmc = 22022 | doi = 10.1073/pnas.96.12.6947 | url = http://www.pnas.org/content/96/12/6947 }}</ref><ref name="pmid16964284">{{cite journal | vauthors = Gamble SC, Chotai D, Odontiadis M, Dart DA, Brooke GN, Powell SM, Reebye V, Varela-Carver A, Kawano Y, Waxman J, Bevan CL | title = Prohibitin, a protein downregulated by androgens, represses androgen receptor activity | journal = Oncogene | volume = 26 | issue = 12 | pages = 1757–68 | date = Mar 2007 | pmid = 16964284 | doi = 10.1038/sj.onc.1209967 }}</ref><ref name="pmid15140878">{{cite journal | vauthors = Kurtev V, Margueron R, Kroboth K, Ogris E, Cavailles V, Seiser C | title = Transcriptional regulation by the repressor of estrogen receptor activity via recruitment of histone deacetylases | journal = The Journal of Biological Chemistry | volume = 279 | issue = 23 | pages = 24834–43 | date = Jun 2004 | pmid = 15140878 | doi = 10.1074/jbc.M312300200 }}</ref><ref name="pmid15713652">{{cite journal | vauthors = Park SE, Xu J, Frolova A, Liao L, O'Malley BW, Katzenellenbogen BS | title = Genetic deletion of the repressor of estrogen receptor activity (REA) enhances the response to estrogen in target tissues in vivo | journal = Molecular and Cellular Biology | volume = 25 | issue = 5 | pages = 1989–99 | date = Mar 2005 | pmid = 15713652 | pmc = 549370 | doi = 10.1128/MCB.25.5.1989-1999.2005 }}</ref>
| citations =  
 
*{{cite journal  | author=McClung JK, Jupe ER, Liu XT, Dell'Orco RT |title=Prohibitin: potential role in senescence, development, and tumor suppression. |journal=Exp. Gerontol. |volume=30 |issue= 2 |pages= 99-124 |year= 1996 |pmid= 8591812 |doi= }}
== Clinical significance ==
*{{cite journal  | author=Dell'Orco RT, McClung JK, Jupe ER, Liu XT |title=Prohibitin and the senescent phenotype. |journal=Exp. Gerontol. |volume=31 |issue= 1-2 |pages= 245-52 |year= 1996 |pmid= 8706794 |doi= }}
 
*{{cite journal  | author=Mishra S, Murphy LC, Nyomba BL, Murphy LJ |title=Prohibitin: a potential target for new therapeutics. |journal=Trends in molecular medicine |volume=11 |issue= 4 |pages= 192-7 |year= 2005 |pmid= 15823758 |doi= 10.1016/j.molmed.2005.02.004 }}
Human prohibitin 1 has some activity as a [[Viral entry#Entry via Membrane Fusion|virus receptor]] protein, having been identified as a receptor for [[Chikungunya|Chikungunya Virus ]] (CHIKV)<ref name="pmid22997079">{{cite journal | vauthors = Wintachai P, Wikan N, Kuadkitkan A, Jaimipuk T, Ubol S, Pulmanausahakul R, Auewarakul P, Kasinrerk W, Weng WY, Panyasrivanit M, Paemanee A, Kittisenachai S, Roytrakul S, Smith DR | title = Identification of prohibitin as a Chikungunya virus receptor protein | journal = Journal of Medical Virology | volume = 84 | issue = 11 | pages = 1757–70 | date = Nov 2012 | pmid = 22997079 | doi = 10.1002/jmv.23403 }}</ref> and [[Dengue Virus]] 2 (DENV-2).<ref name="pmid20674955">{{cite journal | vauthors = Kuadkitkan A, Wikan N, Fongsaran C, Smith DR | title = Identification and characterization of prohibitin as a receptor protein mediating DENV-2 entry into insect cells | journal = Virology | volume = 406 | issue = 1 | pages = 149–61 | date = Oct 2010 | pmid = 20674955 | doi = 10.1016/j.virol.2010.07.015 }}</ref> Little else is known about the activity of the prohibitins in [[viral pathogenesis]].
*{{cite journal | author=Rajalingam K, Rudel T |title=Ras-Raf signaling needs prohibitin. |journal=Cell Cycle |volume=4 |issue= 11 |pages= 1503-5 |year= 2007 |pmid= 16294014 |doi= }}
 
*{{cite journal | author=Sato T, Saito H, Swensen J, ''et al.'' |title=The human prohibitin gene located on chromosome 17q21 is mutated in sporadic breast cancer. |journal=Cancer Res. |volume=52 |issue= 6 |pages= 1643-6 |year= 1992 |pmid= 1540973 |doi= }}
== Interactions ==
*{{cite journal | author=Dawson SJ, White LA |title=Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin. |journal=J. Infect. |volume=24 |issue= 3 |pages= 317-20 |year= 1992 |pmid= 1602151 |doi= }}
 
*{{cite journal  | author=White JJ, Ledbetter DH, Eddy RL, ''et al.'' |title=Assignment of the human prohibitin gene (PHB) to chromosome 17 and identification of a DNA polymorphism. |journal=Genomics |volume=11 |issue= 1 |pages= 228-30 |year= 1992 |pmid= 1684951 |doi= }}
Prohibitin has been shown to [[Protein-protein interaction|interact]] with:
*{{cite journal | author=Altus MS, Wood CM, Stewart DA, ''et al.'' |title=Regions of evolutionary conservation between the rat and human prohibitin-encoding genes. |journal=Gene |volume=158 |issue= 2 |pages= 291-4 |year= 1995 |pmid= 7607556 |doi= }}
{{div col|colwidth=20em}}
*{{cite journal | author=Ikonen E, Fiedler K, Parton RG, Simons K |title=Prohibitin, an antiproliferative protein, is localized to mitochondria. |journal=FEBS Lett. |volume=358 |issue= 3 |pages= 273-7 |year= 1995 |pmid= 7843414 |doi= }}
* [[Annexin A2|ANXA2]]<ref name = pmid12628297>{{cite journal | vauthors = Bacher S, Achatz G, Schmitz ML, Lamers MC | title = Prohibitin and prohibitone are contained in high-molecular weight complexes and interact with alpha-actinin and annexin A2 | journal = Biochimie | volume = 84 | issue = 12 | pages = 1207–20 | date = Dec 2002 | pmid = 12628297 | doi = 10.1016/s0300-9084(02)00027-5 }}</ref>
*{{cite journal | author=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1-2 |pages= 171-4 |year= 1994 |pmid= 8125298 |doi=  }}
* [[C-Raf]],<ref name = pmid10523633>{{cite journal | vauthors = Wang S, Nath N, Fusaro G, Chellappan S | title = Rb and prohibitin target distinct regions of E2F1 for repression and respond to different upstream signals | journal = Molecular and Cellular Biology | volume = 19 | issue = 11 | pages = 7447–60 | date = Nov 1999 | pmid = 10523633 | pmc = 84738 | doi =  10.1128/mcb.19.11.7447}}</ref>
*{{cite journal | author=Sato T, Sakamoto T, Takita K, ''et al.'' |title=The human prohibitin (PHB) gene family and its somatic mutations in human tumors. |journal=Genomics |volume=17 |issue= 3 |pages= 762-4 |year= 1993 |pmid= 8244394 |doi= }}
* [[E2F1]],<ref name = pmid10523633/><ref name = pmid14637159/><ref name = pmid14500729>{{cite journal | vauthors = Fusaro G, Dasgupta P, Rastogi S, Joshi B, Chellappan S | title = Prohibitin induces the transcriptional activity of p53 and is exported from the nucleus upon apoptotic signaling | journal = The Journal of Biological Chemistry | volume = 278 | issue = 48 | pages = 47853–61 | date = Nov 2003 | pmid = 14500729 | doi = 10.1074/jbc.M305171200 }}</ref><ref name = pmid12065415>{{cite journal | vauthors = Wang S, Zhang B, Faller DV | title = Prohibitin requires Brg-1 and Brm for the repression of E2F and cell growth | journal = The EMBO Journal | volume = 21 | issue = 12 | pages = 3019–28 | date = Jun 2002 | pmid = 12065415 | pmc = 126057 | doi = 10.1093/emboj/cdf302 }}</ref>
*{{cite journal | author=Jupe ER, Liu XT, Kiehlbauch JL, ''et al.'' |title=The 3' untranslated region of prohibitin and cellular immortalization. |journal=Exp. Cell Res. |volume=224 |issue= 1 |pages= 128-35 |year= 1996 |pmid= 8612677 |doi= 10.1006/excr.1996.0120 }}
* [[HDAC1]],<ref name = pmid14637159>{{cite journal | vauthors = Joshi B, Ko D, Ordonez-Ercan D, Chellappan SP | title = A putative coiled-coil domain of prohibitin is sufficient to repress E2F1-mediated transcription and induce apoptosis | journal = Biochemical and Biophysical Research Communications | volume = 312 | issue = 2 | pages = 459–66 | date = Dec 2003 | pmid = 14637159 | doi = 10.1016/j.bbrc.2003.10.148 }}</ref><ref name = pmid12466959>{{cite journal | vauthors = Wang S, Fusaro G, Padmanabhan J, Chellappan SP | title = Prohibitin co-localizes with Rb in the nucleus and recruits N-CoR and HDAC1 for transcriptional repression | journal = Oncogene | volume = 21 | issue = 55 | pages = 8388–96 | date = Dec 2002 | pmid = 12466959 | doi = 10.1038/sj.onc.1205944 }}</ref>
*{{cite journal | author=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, ''et al.'' |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1-2 |pages= 149-56 |year= 1997 |pmid= 9373149 |doi= }}
* [[P53]],<ref name = pmid14500729/>
*{{cite journal | author=Rasmussen RK, Ji H, Eddes JS, ''et al.'' |title=Two-dimensional electrophoretic analysis of mixed lineage kinase 2 N-terminal domain binding proteins. |journal=Electrophoresis |volume=19 |issue= 5 |pages= 809-17 |year= 1998 |pmid= 9629920 |doi= 10.1002/elps.1150190535 }}
* [[Retinoblastoma protein|RB1]],<ref name = pmid10523633/><ref name = pmid10376528/>
*{{cite journal  | author=Wang S, Nath N, Adlam M, Chellappan S |title=Prohibitin, a potential tumor suppressor, interacts with RB and regulates E2F function. |journal=Oncogene |volume=18 |issue= 23 |pages= 3501-10 |year= 1999 |pmid= 10376528 |doi= 10.1038/sj.onc.1202684 }}
* [[Retinoblastoma-like protein 1|RBL1]],<ref name = pmid10376528/>
*{{cite journal | author=Wang S, Nath N, Fusaro G, Chellappan S |title=Rb and prohibitin target distinct regions of E2F1 for repression and respond to different upstream signals. |journal=Mol. Cell. Biol. |volume=19 |issue= 11 |pages= 7447-60 |year= 1999 |pmid= 10523633 |doi= }}
* [[Retinoblastoma-like protein 2|RBL2]],<ref name = pmid10376528>{{cite journal | vauthors = Wang S, Nath N, Adlam M, Chellappan S | title = Prohibitin, a potential tumor suppressor, interacts with RB and regulates E2F function | journal = Oncogene | volume = 18 | issue = 23 | pages = 3501–10 | date = Jun 1999 | pmid = 10376528 | doi = 10.1038/sj.onc.1202684 }}</ref>
*{{cite journal | author=Hartley JL, Temple GF, Brasch MA |title=DNA cloning using in vitro site-specific recombination. |journal=Genome Res. |volume=10 |issue= 11 |pages= 1788-95 |year= 2001 |pmid= 11076863 |doi= }}
* [[SMARCA2]],<ref name = pmid12065415/>  and
*{{cite journal | author=Coates PJ, Nenutil R, McGregor A, ''et al.'' |title=Mammalian prohibitin proteins respond to mitochondrial stress and decrease during cellular senescence. |journal=Exp. Cell Res. |volume=265 |issue= 2 |pages= 262-73 |year= 2001 |pmid= 11302691 |doi= 10.1006/excr.2001.5166 }}
* [[SMARCA4]].<ref name = pmid12065415/>
}}
{{Div col end}}
 
==Drugs that bind to prohibitin==
* [[Aurilide]] <ref>{{cite journal | vauthors = Sato S, Murata A, Orihara T, Shirakawa T, Suenaga K, Kigoshi H, Uesugi M | title = Marine natural product aurilide activates the OPA1-mediated apoptosis by binding to prohibitin | journal = Chemistry & Biology | volume = 18 | issue = 1 | pages = 131–9 | date = Jan 2011 | pmid = 21276946 | doi = 10.1016/j.chembiol.2010.10.017 }}</ref>
* [[Fluorizoline]] <ref>{{cite journal | vauthors = Pérez-Perarnau A, Preciado S, Palmeri CM, Moncunill-Massaguer C, Iglesias-Serret D, González-Gironès DM, Miguel M, Karasawa S, Sakamoto S, Cosialls AM, Rubio-Patiño C, Saura-Esteller J, Ramón R, Caja L, Fabregat I, Pons G, Handa H, Albericio F, Gil J, Lavilla R | title = A trifluorinated thiazoline scaffold leading to pro-apoptotic agents targeting prohibitins | journal = Angewandte Chemie | volume = 53 | issue = 38 | pages = 10150–4 | date = Sep 2014 | pmid = 25196378 | doi = 10.1002/anie.201405758 }}</ref><ref>{{cite journal | vauthors = Moncunill-Massaguer C, Saura-Esteller J, Pérez-Perarnau A, Palmeri CM, Núñez-Vázquez S, Cosialls AM, González-Gironès DM, Pomares H, Korwitz A, Preciado S, Albericio F, Lavilla R, Pons G, Langer T, Iglesias-Serret D, Gil J | title = A novel prohibitin-binding compound induces the mitochondrial apoptotic pathway through NOXA and BIM upregulation | journal = Oncotarget | volume = 6 | issue = 39 | pages = 41750–65 | date = Dec 2015 | pmid = 26497683 | doi = 10.18632/oncotarget.6154 | pmc=4747186}}</ref>
* [[Rocaglamide|Rocaglamide A]] <ref>{{cite journal | vauthors = Polier G, Neumann J, Thuaud F, Ribeiro N, Gelhaus C, Schmidt H, Giaisi M, Köhler R, Müller WW, Proksch P, Leippe M, Janssen O, Désaubry L, Krammer PH, Li-Weber M | title = The natural anticancer compounds rocaglamides inhibit the Raf-MEK-ERK pathway by targeting prohibitin 1 and 2 | journal = Chemistry & Biology | volume = 19 | issue = 9 | pages = 1093–104 | date = Sep 2012 | pmid = 22999878 | doi = 10.1016/j.chembiol.2012.07.012 }}</ref>
 
== References ==
{{Reflist|33em}}
 
== Further reading ==
{{refbegin|33em}}
* {{cite journal | vauthors = McClung JK, Jupe ER, Liu XT, Dell'Orco RT | title = Prohibitin: potential role in senescence, development, and tumor suppression | journal = Experimental Gerontology | volume = 30 | issue = 2 | pages = 99–124 | year = 1996 | pmid = 8591812 | doi = 10.1016/0531-5565(94)00069-7 }}
* {{cite journal | vauthors = Dell'Orco RT, McClung JK, Jupe ER, Liu XT | title = Prohibitin and the senescent phenotype | journal = Experimental Gerontology | volume = 31 | issue = 1-2 | pages = 245–52 | year = 1996 | pmid = 8706794 | doi = 10.1016/0531-5565(95)02009-8 }}
* {{cite journal | vauthors = Mishra S, Murphy LC, Nyomba BL, Murphy LJ | title = Prohibitin: a potential target for new therapeutics | journal = Trends in Molecular Medicine | volume = 11 | issue = 4 | pages = 192–7 | date = Apr 2005 | pmid = 15823758 | doi = 10.1016/j.molmed.2005.02.004 }}
* {{cite journal | vauthors = Rajalingam K, Rudel T | title = Ras-Raf signaling needs prohibitin | journal = Cell Cycle | volume = 4 | issue = 11 | pages = 1503–5 | date = Nov 2005 | pmid = 16294014 | doi = 10.4161/cc.4.11.2142 }}
* {{cite journal | vauthors = Sato T, Saito H, Swensen J, Olifant A, Wood C, Danner D, Sakamoto T, Takita K, Kasumi F, Miki Y | title = The human prohibitin gene located on chromosome 17q21 is mutated in sporadic breast cancer | journal = Cancer Research | volume = 52 | issue = 6 | pages = 1643–6 | date = Mar 1992 | pmid = 1540973 | doi =  }}
* {{cite journal | vauthors = Dawson SJ, White LA | title = Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin | journal = The Journal of Infection | volume = 24 | issue = 3 | pages = 317–20 | date = May 1992 | pmid = 1602151 | doi = 10.1016/S0163-4453(05)80037-4 }}
* {{cite journal | vauthors = White JJ, Ledbetter DH, Eddy RL, Shows TB, Stewart DA, Nuell MJ, Friedman V, Wood CM, Owens GA, McClung JK | title = Assignment of the human prohibitin gene (PHB) to chromosome 17 and identification of a DNA polymorphism | journal = Genomics | volume = 11 | issue = 1 | pages = 228–30 | date = Sep 1991 | pmid = 1684951 | doi = 10.1016/0888-7543(91)90126-Y }}
* {{cite journal | vauthors = Altus MS, Wood CM, Stewart DA, Roskams AJ, Friedman V, Henderson T, Owens GA, Danner DB, Jupe ER, Dell'Orco RT | title = Regions of evolutionary conservation between the rat and human prohibitin-encoding genes | journal = Gene | volume = 158 | issue = 2 | pages = 291–4 | date = Jun 1995 | pmid = 7607556 | doi = 10.1016/0378-1119(95)00164-2 }}
* {{cite journal | vauthors = Ikonen E, Fiedler K, Parton RG, Simons K | title = Prohibitin, an antiproliferative protein, is localized to mitochondria | journal = FEBS Letters | volume = 358 | issue = 3 | pages = 273–7 | date = Jan 1995 | pmid = 7843414 | doi = 10.1016/0014-5793(94)01444-6 }}
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1-2 | pages = 171–4 | date = Jan 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
* {{cite journal | vauthors = Sato T, Sakamoto T, Takita K, Saito H, Okui K, Nakamura Y | title = The human prohibitin (PHB) gene family and its somatic mutations in human tumors | journal = Genomics | volume = 17 | issue = 3 | pages = 762–4 | date = Sep 1993 | pmid = 8244394 | doi = 10.1006/geno.1993.1402 }}
* {{cite journal | vauthors = Jupe ER, Liu XT, Kiehlbauch JL, McClung JK, Dell'Orco RT | title = The 3' untranslated region of prohibitin and cellular immortalization | journal = Experimental Cell Research | volume = 224 | issue = 1 | pages = 128–35 | date = Apr 1996 | pmid = 8612677 | doi = 10.1006/excr.1996.0120 }}
* {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1-2 | pages = 149–56 | date = Oct 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
* {{cite journal | vauthors = Rasmussen RK, Ji H, Eddes JS, Moritz RL, Reid GE, Simpson RJ, Dorow DS | title = Two-dimensional electrophoretic analysis of mixed lineage kinase 2 N-terminal domain binding proteins | journal = Electrophoresis | volume = 19 | issue = 5 | pages = 809–17 | date = May 1998 | pmid = 9629920 | doi = 10.1002/elps.1150190535 }}
* {{cite journal | vauthors = Wang S, Nath N, Adlam M, Chellappan S | title = Prohibitin, a potential tumor suppressor, interacts with RB and regulates E2F function | journal = Oncogene | volume = 18 | issue = 23 | pages = 3501–10 | date = Jun 1999 | pmid = 10376528 | doi = 10.1038/sj.onc.1202684 }}
* {{cite journal | vauthors = Wang S, Nath N, Fusaro G, Chellappan S | title = Rb and prohibitin target distinct regions of E2F1 for repression and respond to different upstream signals | journal = Molecular and Cellular Biology | volume = 19 | issue = 11 | pages = 7447–60 | date = Nov 1999 | pmid = 10523633 | pmc = 84738 | doi =  10.1128/mcb.19.11.7447}}
* {{cite journal | vauthors = Hartley JL, Temple GF, Brasch MA | title = DNA cloning using in vitro site-specific recombination | journal = Genome Research | volume = 10 | issue = 11 | pages = 1788–95 | date = Nov 2000 | pmid = 11076863 | pmc = 310948 | doi = 10.1101/gr.143000 }}
* {{cite journal | vauthors = Coates PJ, Nenutil R, McGregor A, Picksley SM, Crouch DH, Hall PA, Wright EG | title = Mammalian prohibitin proteins respond to mitochondrial stress and decrease during cellular senescence | journal = Experimental Cell Research | volume = 265 | issue = 2 | pages = 262–73 | date = May 2001 | pmid = 11302691 | doi = 10.1006/excr.2001.5166 }}
* {{cite journal | vauthors = Van Aken O, Pecenková T, van de Cotte B, De Rycke R, Eeckhout D, Fromm H, De Jaeger G, Witters E, Beemster GT, Inzé D, Van Breusegem F | title = Mitochondrial type-I prohibitins of Arabidopsis thaliana are required for supporting proficient meristem development | journal = The Plant Journal | volume = 52 | issue = 5 | pages = 850–64 | date = Dec 2007 | pmid = 17883375 | doi = 10.1111/j.1365-313X.2007.03276.x }}
{{refend}}
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{{protein-stub}}
[[Category:Genes on human chromosome 17]]

Latest revision as of 14:52, 8 September 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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View/Edit Human

Prohibitin, also known as PHB, is a protein that in humans is encoded by the PHB gene.[1] The Phb gene has also been described in animals, fungi, plants, and unicellular eukaryotes. Prohibitins are divided in two classes, termed Type-I and Type-II prohibitins, based on their similarity to yeast PHB1 and PHB2, respectively. Each organism has at least one copy of each type of prohibitin gene.[2][3]

Discovery

Prohibitins are evolutionarily conserved genes that are ubiquitously expressed. The human prohibitin gene, located on the BRCA1 chromosome region 17q21, was originally thought to be a negative regulator of cell proliferation and a tumor suppressor. This anti-proliferative activity was later attributed to the 3' UTR of the PHB gene, and not to the actual protein. Mutations in human PHB have been linked to sporadic breast cancer. However, over-expression of PHB has been associated with a reduction in the androgen receptor activity and a reduction in PSA gene expression resulting in a decrease of androgen-dependent growth of cancerous prostate cells.[4] Prohibitin is expressed as two transcripts with varying lengths of 3' untranslated region. The longer transcript is present at higher levels in proliferating tissues and cells, suggesting that this longer 3' untranslated region may function as a trans-acting regulatory RNA.[1]

Function

Prohibitins may have multiple functions including:

Mitochondrial function and morphology

Prohibitins are assembled into a ring-like structure with 16–20 alternating Phb1 and Phb2 subunits in the inner mitochondrial membrane.[5] The precise molecular function of the PHB complex is not clear, but a role as chaperone for respiration chain proteins or as a general structuring scaffold required for optimal mitochondrial morphology and function are suspected. Recently, prohibitins have been demonstrated to be positive, rather than negative, regulators of cell proliferation in both plants and mice.

Transcriptional modulation

Both human prohibitins have also been suggested to be localized in the nucleus and modulate transcriptional activity by interacting with various transcription factors, including nuclear receptors, either directly or indirectly. However, little evidence for nuclear targeting and transcription factor-binding of prohibitins has been found in other organism (yeast, plants, C. elegans, etc.), indicating that this may be a specific function in mammalian cells.[6][7][8][9]

Clinical significance

Human prohibitin 1 has some activity as a virus receptor protein, having been identified as a receptor for Chikungunya Virus (CHIKV)[10] and Dengue Virus 2 (DENV-2).[11] Little else is known about the activity of the prohibitins in viral pathogenesis.

Interactions

Prohibitin has been shown to interact with:

Drugs that bind to prohibitin

References

  1. ↑ 1.0 1.1 "Entrez Gene: PHB prohibitin".
  2. ↑ Van Aken O, Pecenková T, van de Cotte B, De Rycke R, Eeckhout D, Fromm H, De Jaeger G, Witters E, Beemster GT, Inzé D, Van Breusegem F (Dec 2007). "Mitochondrial type-I prohibitins of Arabidopsis thaliana are required for supporting proficient meristem development". The Plant Journal. 52 (5): 850–64. doi:10.1111/j.1365-313X.2007.03276.x. PMID 17883375.
  3. ↑ Mishra S, Murphy LC, Murphy LJ (2006). "The Prohibitins: emerging roles in diverse functions". Journal of Cellular and Molecular Medicine. 10 (2): 353–63. doi:10.1111/j.1582-4934.2006.tb00404.x. PMID 16796804.
  4. ↑ Dart, D Alwyn. "Manipulating prohibitin levels provides evidence for an in vivo role in androgen regulation of prostate tumours". Endocr Relat Cancer. PMC 2782800. Missing or empty |url= (help)
  5. ↑ Tatsuta T, Model K, Langer T (Jan 2005). "Formation of membrane-bound ring complexes by prohibitins in mitochondria". Molecular Biology of the Cell. 16 (1): 248–59. doi:10.1091/mbc.E04-09-0807. PMC 539169. PMID 15525670.
  6. ↑ Montano MM, Ekena K, Delage-Mourroux R, Chang W, Martini P, Katzenellenbogen BS (Jun 1999). "An estrogen receptor-selective coregulator that potentiates the effectiveness of antiestrogens and represses the activity of estrogens". Proceedings of the National Academy of Sciences of the United States of America. 96 (12): 6947–52. doi:10.1073/pnas.96.12.6947. PMC 22022. PMID 10359819.
  7. ↑ Gamble SC, Chotai D, Odontiadis M, Dart DA, Brooke GN, Powell SM, Reebye V, Varela-Carver A, Kawano Y, Waxman J, Bevan CL (Mar 2007). "Prohibitin, a protein downregulated by androgens, represses androgen receptor activity". Oncogene. 26 (12): 1757–68. doi:10.1038/sj.onc.1209967. PMID 16964284.
  8. ↑ Kurtev V, Margueron R, Kroboth K, Ogris E, Cavailles V, Seiser C (Jun 2004). "Transcriptional regulation by the repressor of estrogen receptor activity via recruitment of histone deacetylases". The Journal of Biological Chemistry. 279 (23): 24834–43. doi:10.1074/jbc.M312300200. PMID 15140878.
  9. ↑ Park SE, Xu J, Frolova A, Liao L, O'Malley BW, Katzenellenbogen BS (Mar 2005). "Genetic deletion of the repressor of estrogen receptor activity (REA) enhances the response to estrogen in target tissues in vivo". Molecular and Cellular Biology. 25 (5): 1989–99. doi:10.1128/MCB.25.5.1989-1999.2005. PMC 549370. PMID 15713652.
  10. ↑ Wintachai P, Wikan N, Kuadkitkan A, Jaimipuk T, Ubol S, Pulmanausahakul R, Auewarakul P, Kasinrerk W, Weng WY, Panyasrivanit M, Paemanee A, Kittisenachai S, Roytrakul S, Smith DR (Nov 2012). "Identification of prohibitin as a Chikungunya virus receptor protein". Journal of Medical Virology. 84 (11): 1757–70. doi:10.1002/jmv.23403. PMID 22997079.
  11. ↑ Kuadkitkan A, Wikan N, Fongsaran C, Smith DR (Oct 2010). "Identification and characterization of prohibitin as a receptor protein mediating DENV-2 entry into insect cells". Virology. 406 (1): 149–61. doi:10.1016/j.virol.2010.07.015. PMID 20674955.
  12. ↑ Bacher S, Achatz G, Schmitz ML, Lamers MC (Dec 2002). "Prohibitin and prohibitone are contained in high-molecular weight complexes and interact with alpha-actinin and annexin A2". Biochimie. 84 (12): 1207–20. doi:10.1016/s0300-9084(02)00027-5. PMID 12628297.
  13. ↑ 13.0 13.1 13.2 Wang S, Nath N, Fusaro G, Chellappan S (Nov 1999). "Rb and prohibitin target distinct regions of E2F1 for repression and respond to different upstream signals". Molecular and Cellular Biology. 19 (11): 7447–60. doi:10.1128/mcb.19.11.7447. PMC 84738. PMID 10523633.
  14. ↑ 14.0 14.1 Joshi B, Ko D, Ordonez-Ercan D, Chellappan SP (Dec 2003). "A putative coiled-coil domain of prohibitin is sufficient to repress E2F1-mediated transcription and induce apoptosis". Biochemical and Biophysical Research Communications. 312 (2): 459–66. doi:10.1016/j.bbrc.2003.10.148. PMID 14637159.
  15. ↑ 15.0 15.1 Fusaro G, Dasgupta P, Rastogi S, Joshi B, Chellappan S (Nov 2003). "Prohibitin induces the transcriptional activity of p53 and is exported from the nucleus upon apoptotic signaling". The Journal of Biological Chemistry. 278 (48): 47853–61. doi:10.1074/jbc.M305171200. PMID 14500729.
  16. ↑ 16.0 16.1 16.2 Wang S, Zhang B, Faller DV (Jun 2002). "Prohibitin requires Brg-1 and Brm for the repression of E2F and cell growth". The EMBO Journal. 21 (12): 3019–28. doi:10.1093/emboj/cdf302. PMC 126057. PMID 12065415.
  17. ↑ Wang S, Fusaro G, Padmanabhan J, Chellappan SP (Dec 2002). "Prohibitin co-localizes with Rb in the nucleus and recruits N-CoR and HDAC1 for transcriptional repression". Oncogene. 21 (55): 8388–96. doi:10.1038/sj.onc.1205944. PMID 12466959.
  18. ↑ 18.0 18.1 18.2 Wang S, Nath N, Adlam M, Chellappan S (Jun 1999). "Prohibitin, a potential tumor suppressor, interacts with RB and regulates E2F function". Oncogene. 18 (23): 3501–10. doi:10.1038/sj.onc.1202684. PMID 10376528.
  19. ↑ Sato S, Murata A, Orihara T, Shirakawa T, Suenaga K, Kigoshi H, Uesugi M (Jan 2011). "Marine natural product aurilide activates the OPA1-mediated apoptosis by binding to prohibitin". Chemistry & Biology. 18 (1): 131–9. doi:10.1016/j.chembiol.2010.10.017. PMID 21276946.
  20. ↑ Pérez-Perarnau A, Preciado S, Palmeri CM, Moncunill-Massaguer C, Iglesias-Serret D, González-Gironès DM, Miguel M, Karasawa S, Sakamoto S, Cosialls AM, Rubio-Patiño C, Saura-Esteller J, Ramón R, Caja L, Fabregat I, Pons G, Handa H, Albericio F, Gil J, Lavilla R (Sep 2014). "A trifluorinated thiazoline scaffold leading to pro-apoptotic agents targeting prohibitins". Angewandte Chemie. 53 (38): 10150–4. doi:10.1002/anie.201405758. PMID 25196378.
  21. ↑ Moncunill-Massaguer C, Saura-Esteller J, Pérez-Perarnau A, Palmeri CM, Núñez-Vázquez S, Cosialls AM, González-Gironès DM, Pomares H, Korwitz A, Preciado S, Albericio F, Lavilla R, Pons G, Langer T, Iglesias-Serret D, Gil J (Dec 2015). "A novel prohibitin-binding compound induces the mitochondrial apoptotic pathway through NOXA and BIM upregulation". Oncotarget. 6 (39): 41750–65. doi:10.18632/oncotarget.6154. PMC 4747186. PMID 26497683.
  22. ↑ Polier G, Neumann J, Thuaud F, Ribeiro N, Gelhaus C, Schmidt H, Giaisi M, Köhler R, Müller WW, Proksch P, Leippe M, Janssen O, Désaubry L, Krammer PH, Li-Weber M (Sep 2012). "The natural anticancer compounds rocaglamides inhibit the Raf-MEK-ERK pathway by targeting prohibitin 1 and 2". Chemistry & Biology. 19 (9): 1093–104. doi:10.1016/j.chembiol.2012.07.012. PMID 22999878.

Further reading

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