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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''Histone deacetylase 8''' is an [[enzyme]] that in humans is encoded by the ''HDAC8'' [[gene]].<ref name="pmid10756090">{{cite journal |vauthors=McDonell N, Ramser J, Francis F, Vinet MC, Rider S, Sudbrak R, Riesselman L, Yaspo ML, Reinhardt R, Monaco AP, Ross F, Kahn A, Kearney L, Buckle V, Chelly J | title = Characterization of a highly complex region in Xq13 and mapping of three isodicentric breakpoints associated with preleukemia | journal = Genomics | volume = 64 | issue = 3 | pages = 221–9 |date=May 2000 | pmid = 10756090 | pmc =  | doi = 10.1006/geno.2000.6128 }}</ref><ref name="pmid10922473">{{cite journal |vauthors=Van den Wyngaert I, de Vries W, Kremer A, Neefs J, Verhasselt P, Luyten WH, Kass SU | title = Cloning and characterization of human histone deacetylase 8 | journal = FEBS Lett | volume = 478 | issue = 1–2 | pages = 77–83 |date=Aug 2000 | pmid = 10922473 | pmc =  | doi =10.1016/S0014-5793(00)01813-5  }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: HDAC8 histone deacetylase 8| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=55869| accessdate = }}</ref>
| update_page = yes
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| update_protein_box = yes
| update_summary = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image = PBB_Protein_HDAC8_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1t64.
| PDB = {{PDB2|1t64}}, {{PDB2|1t67}}, {{PDB2|1t69}}, {{PDB2|1vkg}}, {{PDB2|1w22}}
| Name = Histone deacetylase 8
| HGNCid = 13315
| Symbol = HDAC8
| AltSymbols =; RPD3; HDACL1
| OMIM = 300269
| ECnumber = 
| Homologene = 41274
| MGIid = 1917565
| Function = {{GNF_GO|id=GO:0004407 |text = histone deacetylase activity}} {{GNF_GO|id=GO:0008134 |text = transcription factor binding}} {{GNF_GO|id=GO:0016787 |text = hydrolase activity}}
| Component = {{GNF_GO|id=GO:0000118 |text = histone deacetylase complex}} {{GNF_GO|id=GO:0000228 |text = nuclear chromosome}} {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005737 |text = cytoplasm}}
| Process = {{GNF_GO|id=GO:0000122 |text = negative regulation of transcription from RNA polymerase II promoter}} {{GNF_GO|id=GO:0006333 |text = chromatin assembly or disassembly}} {{GNF_GO|id=GO:0006350 |text = transcription}} {{GNF_GO|id=GO:0006355 |text = regulation of transcription, DNA-dependent}} {{GNF_GO|id=GO:0016568 |text = chromatin modification}} {{GNF_GO|id=GO:0016575 |text = histone deacetylation}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 55869
    | Hs_Ensembl = ENSG00000147099
    | Hs_RefseqProtein = NP_060956
    | Hs_RefseqmRNA = NM_018486
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = X
    | Hs_GenLoc_start = 71466091
    | Hs_GenLoc_end = 71709623
    | Hs_Uniprot = Q9BY41
    | Mm_EntrezGene = 70315
    | Mm_Ensembl = ENSMUSG00000067567
    | Mm_RefseqmRNA = NM_027382
    | Mm_RefseqProtein = NP_081658
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = X
    | Mm_GenLoc_start = 98510356
    | Mm_GenLoc_end = 98707783
    | Mm_Uniprot = Q8VH37
  }}
}}
'''Histone deacetylase 8''', also known as '''HDAC8''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: HDAC8 histone deacetylase 8| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=55869| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
[[Histone]]s play a critical role in [[transcriptional regulation]], [[cell cycle]] progression, and developmental events. Histone [[acetylation]] / deacetylation alters [[chromosome]] structure and affects [[transcription factor]] access to DNA. The protein encoded by this gene belongs to class I of the histone deacetylase/acuc/apha family. It has histone deacetylase activity and represses transcription when tethered to a [[promoter (genetics)|promoter]].<ref name="entrez"/>
{{PBB_Summary
 
| section_title =
Histone deacetylase 8 is involved in skull [[morphogenesis]]<ref name="pmid19605684">{{cite journal |vauthors=Haberland M, Mokalled MH, Montgomery RL, Olson EN | title = Epigenetic control of skull morphogenesis by histone deacetylase 8 | journal = Genes Dev. | volume = 23 | issue = 14 | pages = 1625–30 |date=July 2009 | pmid = 19605684 | pmc = 2714711 | doi = 10.1101/gad.1809209 }}</ref> and metabolic control of the [[Estrogen-related receptor alpha|ERR-alpha]] / [[PPARGC1A|PGC1-alpha]] transcriptional complex.<ref name="pmid20484414">{{cite journal |vauthors=Wilson BJ, Tremblay AM, Deblois G, Sylvain-Drolet G, Giguère V | title = An acetylation switch modulates the transcriptional activity of estrogen-related receptor alpha | journal = Mol. Endocrinol. | volume = 24 | issue = 7 | pages = 1349–58 |date=July 2010 | pmid = 20484414 | pmc = 5417470 | doi = 10.1210/me.2009-0441 }}</ref>
| summary_text = Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to class I of the histone deacetylase/acuc/apha family. It has histone deacetylase activity and represses transcription when tethered to a promoter.<ref name="entrez">{{cite web | title = Entrez Gene: HDAC8 histone deacetylase 8| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=55869| accessdate = }}</ref>
 
}}
== Clinical significance ==
 
HDAC8 has been linked to number of disease states notably to [[acute myeloid leukemia]] and is related to actin cytoskeleton in smooth muscle cells. [[siRNA]] targeting HDAC8 showed anticancer effects.<ref name="pmid17325692">{{cite journal |vauthors=Gallinari P, Di Marco S, Jones P, Pallaoro M, Steinkühler C | title = HDACs, histone deacetylation and gene transcription: from molecular biology to cancer therapeutics | journal = Cell Res. | volume = 17 | issue = 3 | pages = 195–211 |date=March 2007 | pmid = 17325692 | doi = 10.1038/sj.cr.7310149 }}</ref> Inhibition of HDAC8 induced apoptosis has been observed in [[T-cell lymphomas|T cell lymphomas]].<ref name="pmid18256683">{{cite journal |vauthors=Balasubramanian S, Ramos J, Luo W, Sirisawad M, Verner E, Buggy JJ | title = A novel histone deacetylase 8 (HDAC8)-specific inhibitor PCI-34051 induces apoptosis in T-cell lymphomas | journal = Leukemia | volume = 22 | issue = 5 | pages = 1026–34 |date=May 2008 | pmid = 18256683 | doi = 10.1038/leu.2008.9 }}</ref> In addition the HDAC8 enzyme has been implicated in the pathogenesis of [[neuroblastoma]].<ref name="pmid19118036">{{cite journal |vauthors=Oehme I, Deubzer HE, Wegener D, Pickert D, Linke JP, Hero B, Kopp-Schneider A, Westermann F, Ulrich SM, von Deimling A, Fischer M, Witt O | title = Histone deacetylase 8 in neuroblastoma tumorigenesis | journal = Clin. Cancer Res. | volume = 15 | issue = 1 | pages = 91–9 |date=January 2009 | pmid = 19118036 | doi = 10.1158/1078-0432.CCR-08-0684 }}</ref> Therefore, there has been interest in developing HDAC8 selective inhibitors.<ref name="pmid23547652">{{cite journal |vauthors=Patil V, Sodji QH, Kornacki JR, Mrksich M, Oyelere AK | title = 3-Hydroxypyridin-2-thione as novel zinc binding group for selective histone deacetylase inhibition | journal = Journal of Medicinal Chemistry | volume = 56 | issue = 9 | pages = 3492–506 |date=May 2013 | pmid = 23547652 | doi = 10.1021/jm301769u | pmc=3657749}}</ref><ref name="pmid23116147">{{cite journal |vauthors=Suzuki T, Ota Y, Ri M, Bando M, Gotoh A, Itoh Y, Tsumoto H, Tatum PR, Mizukami T, Nakagawa H, Iida S, Ueda R, Shirahige K, Miyata N | title = Rapid discovery of highly potent and selective inhibitors of histone deacetylase 8 using click chemistry to generate candidate libraries | journal = Journal of Medicinal Chemistry | volume = 55 | issue = 22 | pages = 9562–75 |date=November 2012 | pmid = 23116147 | doi = 10.1021/jm300837y }}</ref>
 
==Interactions==
* [[ERR-alpha]].<ref name=pmid20484414/>


==See also==
==See also==
* [[Histone deacetylase]]
* [[Histone deacetylase]]
{{Clear}}


==References==
==References==
{{reflist|2}}
{{reflist|35em}}


==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin|35em}}
{{PBB_Further_reading
*{{cite journal  |vauthors=Waltregny D, De Leval L, Glénisson W, Ly Tran S, North BJ, Bellahcène A, Weidle U, Verdin E, Castronovo V |title= Expression of histone deacetylase 8, a class I histone deacetylase, is restricted to cells showing smooth muscle differentiation in normal human tissues|journal=Am J Pathol |pmid= 15277229  | year= 2004  | volume= 165  | issue= 2  | pages= 553–64  | pmc= 1618574  | doi= 10.1016/S0002-9440(10)63320-2 }}
| citations =
*{{cite journal  | pmid= 15772115  |vauthors=Glénisson W, Waltregny D, Tran SL, North BJ, Verdin E, Colige A, Castronovo V |title= Histone deacetylase HDAC8 associates with smooth muscle alpha-actin and is essential for smooth muscle cell contractility|journal=FASEB J. |doi=10.1096/fj.04-2303fje |volume=19 |issue=8 |date=June 2005 |pages=966–8}}
*{{cite journal  | author=Verdin E, Dequiedt F, Kasler HG |title=Class II histone deacetylases: versatile regulators. |journal=Trends Genet. |volume=19 |issue= 5 |pages= 286-93 |year= 2003 |pmid= 12711221 |doi= }}
*{{cite journal  |vauthors=Wedel T, Van Eys GJ, Waltregny D, Glénisson W, Castronovo V, Vanderwinden JM |title=Novel smooth muscle markers reveal abnormalities of the intestinal musculature in severe colorectal motility disorders|journal=Neurogastroenterol. Motil. |pmid= 16771768  | year= 2006  | volume= 18  | issue= 7  | pages= 526–38  | doi= 10.1111/j.1365-2982.2006.00781.x}}
*{{cite journal  | author=Hu E, Chen Z, Fredrickson T, ''et al.'' |title=Cloning and characterization of a novel human class I histone deacetylase that functions as a transcription repressor. |journal=J. Biol. Chem. |volume=275 |issue= 20 |pages= 15254-64 |year= 2000 |pmid= 10748112 |doi= 10.1074/jbc.M908988199 }}
*{{cite journal  |vauthors=Verdin E, Dequiedt F, Kasler HG |title=Class II histone deacetylases: versatile regulators |journal=Trends Genet. |volume=19 |issue= 5 |pages= 286–93 |year= 2003 |pmid= 12711221 |doi=10.1016/S0168-9525(03)00073-8 |citeseerx=10.1.1.464.415 }}
*{{cite journal  | author=McDonell N, Ramser J, Francis F, ''et al.'' |title=Characterization of a highly complex region in Xq13 and mapping of three isodicentric breakpoints associated with preleukemia. |journal=Genomics |volume=64 |issue= 3 |pages= 221-9 |year= 2000 |pmid= 10756090 |doi= 10.1006/geno.2000.6128 }}
*{{cite journal   |vauthors=Hu E, Chen Z, Fredrickson T, etal |title=Cloning and characterization of a novel human class I histone deacetylase that functions as a transcription repressor |journal=J. Biol. Chem. |volume=275 |issue= 20 |pages= 15254–64 |year= 2000 |pmid= 10748112 |doi= 10.1074/jbc.M908988199 }}
*{{cite journal  | author=Van den Wyngaert I, de Vries W, Kremer A, ''et al.'' |title=Cloning and characterization of human histone deacetylase 8. |journal=FEBS Lett. |volume=478 |issue= 1-2 |pages= 77-83 |year= 2000 |pmid= 10922473 |doi=  }}
*{{cite journal   |vauthors=Buggy JJ, Sideris ML, Mak P, etal |title=Cloning and characterization of a novel human histone deacetylase, HDAC8 |journal=Biochem. J. |volume=350 |issue= 1|pages= 199–205 |year= 2001 |pmid= 10926844 |doi= 10.1042/0264-6021:3500199| pmc=1221242 }}
*{{cite journal | author=Buggy JJ, Sideris ML, Mak P, ''et al.'' |title=Cloning and characterization of a novel human histone deacetylase, HDAC8. |journal=Biochem. J. |volume=350 Pt 1 |issue= |pages= 199-205 |year= 2001 |pmid= 10926844 |doi= }}
*{{cite journal   |vauthors=Amann JM, Nip J, Strom DK, etal |title=ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain |journal=Mol. Cell. Biol. |volume=21 |issue= 19 |pages= 6470–83 |year= 2001 |pmid= 11533236 |doi=10.1128/MCB.21.19.6470-6483.2001  | pmc=99794  }}
*{{cite journal | author=Amann JM, Nip J, Strom DK, ''et al.'' |title=ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain. |journal=Mol. Cell. Biol. |volume=21 |issue= 19 |pages= 6470-83 |year= 2001 |pmid= 11533236 |doi=  }}
*{{cite journal   |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal   |vauthors=Durst KL, Lutterbach B, Kummalue T, etal |title=The inv(16) fusion protein associates with corepressors via a smooth muscle myosin heavy-chain domain |journal=Mol. Cell. Biol. |volume=23 |issue= 2 |pages= 607–19 |year= 2003 |pmid= 12509458 |doi=10.1128/MCB.23.2.607-619.2003  | pmc=151524  }}
*{{cite journal | author=Durst KL, Lutterbach B, Kummalue T, ''et al.'' |title=The inv(16) fusion protein associates with corepressors via a smooth muscle myosin heavy-chain domain. |journal=Mol. Cell. Biol. |volume=23 |issue= 2 |pages= 607-19 |year= 2003 |pmid= 12509458 |doi=  }}
*{{cite journal  |vauthors=Rodriguez M, Yu X, Chen J, Songyang Z |title=Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains |journal=J. Biol. Chem. |volume=278 |issue= 52 |pages= 52914–8 |year= 2004 |pmid= 14578343 |doi= 10.1074/jbc.C300407200 }}
*{{cite journal | author=Rodriguez M, Yu X, Chen J, Songyang Z |title=Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains. |journal=J. Biol. Chem. |volume=278 |issue= 52 |pages= 52914-8 |year= 2004 |pmid= 14578343 |doi= 10.1074/jbc.C300407200 }}
*{{cite journal   |vauthors=Johnson JM, Castle J, Garrett-Engele P, etal |title=Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays |journal=Science |volume=302 |issue= 5653 |pages= 2141–4 |year= 2004 |pmid= 14684825 |doi= 10.1126/science.1090100 |citeseerx=10.1.1.1017.9438 }}
*{{cite journal  | author=Johnson JM, Castle J, Garrett-Engele P, ''et al.'' |title=Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays. |journal=Science |volume=302 |issue= 5653 |pages= 2141-4 |year= 2004 |pmid= 14684825 |doi= 10.1126/science.1090100 }}
*{{cite journal  |vauthors=Lee H, Rezai-Zadeh N, Seto E |title=Negative regulation of histone deacetylase 8 activity by cyclic AMP-dependent protein kinase A |journal=Mol. Cell. Biol. |volume=24 |issue= 2 |pages= 765–73 |year= 2004 |pmid= 14701748 |doi=10.1128/MCB.24.2.765-773.2004  | pmc=343812  }}
*{{cite journal | author=Lee H, Rezai-Zadeh N, Seto E |title=Negative regulation of histone deacetylase 8 activity by cyclic AMP-dependent protein kinase A. |journal=Mol. Cell. Biol. |volume=24 |issue= 2 |pages= 765-73 |year= 2004 |pmid= 14701748 |doi= }}
*{{cite journal   |vauthors=Vannini A, Volpari C, Filocamo G, etal |title=Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue= 42 |pages= 15064–9 |year= 2004 |pmid= 15477595 |doi= 10.1073/pnas.0404603101 | pmc=524051 }}
*{{cite journal  | author=Vannini A, Volpari C, Filocamo G, ''et al.'' |title=Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue= 42 |pages= 15064-9 |year= 2004 |pmid= 15477595 |doi= 10.1073/pnas.0404603101 }}
*{{cite journal   |vauthors=Waltregny D, North B, Van Mellaert F, etal |title=Screening of histone deacetylases (HDAC) expression in human prostate cancer reveals distinct class I HDAC profiles between epithelial and stromal cells |journal=European Journal of Histochemistry |volume=48 |issue= 3 |pages= 273–90 |year= 2005 |pmid= 15590418 |doi= }}
*{{cite journal | author=Waltregny D, North B, Van Mellaert F, ''et al.'' |title=Screening of histone deacetylases (HDAC) expression in human prostate cancer reveals distinct class I HDAC profiles between epithelial and stromal cells. |journal=European journal of histochemistry : EJH |volume=48 |issue= 3 |pages= 273-90 |year= 2005 |pmid= 15590418 |doi=  }}
*{{cite journal   |vauthors=Waltregny D, Glénisson W, Tran SL, etal |title=Histone deacetylase HDAC8 associates with smooth muscle alpha-actin and is essential for smooth muscle cell contractility |journal=FASEB J. |volume=19 |issue= 8 |pages= 966–8 |year= 2006 |pmid= 15772115 |doi= 10.1096/fj.04-2303fje }}
*{{cite journal | author=Waltregny D, Glénisson W, Tran SL, ''et al.'' |title=Histone deacetylase HDAC8 associates with smooth muscle alpha-actin and is essential for smooth muscle cell contractility. |journal=FASEB J. |volume=19 |issue= 8 |pages= 966-8 |year= 2006 |pmid= 15772115 |doi= 10.1096/fj.04-2303fje }}
*{{cite journal  |vauthors=Gantt SL, Gattis SG, Fierke CA |title=Catalytic activity and inhibition of human histone deacetylase 8 is dependent on the identity of the active site metal ion |journal=Biochemistry |volume=45 |issue= 19 |pages= 6170–8 |year= 2006 |pmid= 16681389 |doi= 10.1021/bi060212u }}
*{{cite journal | author=Gantt SL, Gattis SG, Fierke CA |title=Catalytic activity and inhibition of human histone deacetylase 8 is dependent on the identity of the active site metal ion. |journal=Biochemistry |volume=45 |issue= 19 |pages= 6170-8 |year= 2006 |pmid= 16681389 |doi= 10.1021/bi060212u }}
*{{cite journal   |vauthors=Lee H, Sengupta N, Villagra A, etal |title=Histone deacetylase 8 safeguards the human ever-shorter telomeres 1B (hEST1B) protein from ubiquitin-mediated degradation |journal=Mol. Cell. Biol. |volume=26 |issue= 14 |pages= 5259–69 |year= 2006 |pmid= 16809764 |doi= 10.1128/MCB.01971-05  | pmc=1592721 }}
*{{cite journal  | author=Lee H, Sengupta N, Villagra A, ''et al.'' |title=Histone deacetylase 8 safeguards the human ever-shorter telomeres 1B (hEST1B) protein from ubiquitin-mediated degradation. |journal=Mol. Cell. Biol. |volume=26 |issue= 14 |pages= 5259-69 |year= 2006 |pmid= 16809764 |doi= 10.1128/MCB.01971-05 }}
*{{cite journal  |vauthors=Vannini A, Volpari C, Gallinari P, etal |title=Substrate binding to histone deacetylases as shown by the crystal structure of the HDAC8-substrate complex |journal=EMBO Reports |volume=8 |issue= 9 |pages= 879–84 |year= 2007 |pmid= 17721440 |doi= 10.1038/sj.embor.7401047 | pmc=1973954 }}
*{{cite journal | author=Vannini A, Volpari C, Gallinari P, ''et al.'' |title=Substrate binding to histone deacetylases as shown by the crystal structure of the HDAC8-substrate complex. |journal=EMBO Rep. |volume=8 |issue= 9 |pages= 879-84 |year= 2007 |pmid= 17721440 |doi= 10.1038/sj.embor.7401047 }}
*{{cite journal   |vauthors=Nakagawa M, Oda Y, Eguchi T, etal |title=Expression profile of class I histone deacetylases in human cancer tissues |journal=Oncol. Rep. |volume=18 |issue= 4 |pages= 769–74 |year= 2007 |pmid= 17786334 |doi=  10.3892/or.18.4.769}}
*{{cite journal | author=Nakagawa M, Oda Y, Eguchi T, ''et al.'' |title=Expression profile of class I histone deacetylases in human cancer tissues. |journal=Oncol. Rep. |volume=18 |issue= 4 |pages= 769-74 |year= 2007 |pmid= 17786334 |doi=  }}
}}
{{refend}}
{{refend}}


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* {{MeshName|HDAC8+protein,+human}}
* {{MeshName|HDAC8+protein,+human}}


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Latest revision as of 23:55, 5 September 2018

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

Histone deacetylase 8 is an enzyme that in humans is encoded by the HDAC8 gene.[1][2][3]

Function

Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation / deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to class I of the histone deacetylase/acuc/apha family. It has histone deacetylase activity and represses transcription when tethered to a promoter.[3]

Histone deacetylase 8 is involved in skull morphogenesis[4] and metabolic control of the ERR-alpha / PGC1-alpha transcriptional complex.[5]

Clinical significance

HDAC8 has been linked to number of disease states notably to acute myeloid leukemia and is related to actin cytoskeleton in smooth muscle cells. siRNA targeting HDAC8 showed anticancer effects.[6] Inhibition of HDAC8 induced apoptosis has been observed in T cell lymphomas.[7] In addition the HDAC8 enzyme has been implicated in the pathogenesis of neuroblastoma.[8] Therefore, there has been interest in developing HDAC8 selective inhibitors.[9][10]

Interactions

See also

References

  1. ↑ McDonell N, Ramser J, Francis F, Vinet MC, Rider S, Sudbrak R, Riesselman L, Yaspo ML, Reinhardt R, Monaco AP, Ross F, Kahn A, Kearney L, Buckle V, Chelly J (May 2000). "Characterization of a highly complex region in Xq13 and mapping of three isodicentric breakpoints associated with preleukemia". Genomics. 64 (3): 221–9. doi:10.1006/geno.2000.6128. PMID 10756090.
  2. ↑ Van den Wyngaert I, de Vries W, Kremer A, Neefs J, Verhasselt P, Luyten WH, Kass SU (Aug 2000). "Cloning and characterization of human histone deacetylase 8". FEBS Lett. 478 (1–2): 77–83. doi:10.1016/S0014-5793(00)01813-5. PMID 10922473.
  3. ↑ 3.0 3.1 "Entrez Gene: HDAC8 histone deacetylase 8".
  4. ↑ Haberland M, Mokalled MH, Montgomery RL, Olson EN (July 2009). "Epigenetic control of skull morphogenesis by histone deacetylase 8". Genes Dev. 23 (14): 1625–30. doi:10.1101/gad.1809209. PMC 2714711. PMID 19605684.
  5. ↑ 5.0 5.1 Wilson BJ, Tremblay AM, Deblois G, Sylvain-Drolet G, Giguère V (July 2010). "An acetylation switch modulates the transcriptional activity of estrogen-related receptor alpha". Mol. Endocrinol. 24 (7): 1349–58. doi:10.1210/me.2009-0441. PMC 5417470. PMID 20484414.
  6. ↑ Gallinari P, Di Marco S, Jones P, Pallaoro M, Steinkühler C (March 2007). "HDACs, histone deacetylation and gene transcription: from molecular biology to cancer therapeutics". Cell Res. 17 (3): 195–211. doi:10.1038/sj.cr.7310149. PMID 17325692.
  7. ↑ Balasubramanian S, Ramos J, Luo W, Sirisawad M, Verner E, Buggy JJ (May 2008). "A novel histone deacetylase 8 (HDAC8)-specific inhibitor PCI-34051 induces apoptosis in T-cell lymphomas". Leukemia. 22 (5): 1026–34. doi:10.1038/leu.2008.9. PMID 18256683.
  8. ↑ Oehme I, Deubzer HE, Wegener D, Pickert D, Linke JP, Hero B, Kopp-Schneider A, Westermann F, Ulrich SM, von Deimling A, Fischer M, Witt O (January 2009). "Histone deacetylase 8 in neuroblastoma tumorigenesis". Clin. Cancer Res. 15 (1): 91–9. doi:10.1158/1078-0432.CCR-08-0684. PMID 19118036.
  9. ↑ Patil V, Sodji QH, Kornacki JR, Mrksich M, Oyelere AK (May 2013). "3-Hydroxypyridin-2-thione as novel zinc binding group for selective histone deacetylase inhibition". Journal of Medicinal Chemistry. 56 (9): 3492–506. doi:10.1021/jm301769u. PMC 3657749. PMID 23547652.
  10. ↑ Suzuki T, Ota Y, Ri M, Bando M, Gotoh A, Itoh Y, Tsumoto H, Tatum PR, Mizukami T, Nakagawa H, Iida S, Ueda R, Shirahige K, Miyata N (November 2012). "Rapid discovery of highly potent and selective inhibitors of histone deacetylase 8 using click chemistry to generate candidate libraries". Journal of Medicinal Chemistry. 55 (22): 9562–75. doi:10.1021/jm300837y. PMID 23116147.

Further reading

External links

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