HDAC8

HDAC8
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1T64, 1T67, 1T69, 1VKG, 1W22, 2V5W, 2V5X, 3EW8, 3EWF, 3EZP, 3EZT, 3F06, 3F07, 3F0R, 3MZ3, 3MZ4, 3MZ6, 3MZ7, 3RQD, 3SFF, 3SFH, 4QA0, 4QA1, 4QA2, 4QA3, 4QA4, 4QA5, 4QA6, 4QA7, 4RN0, 4RN1, 4RN2, 5DC7, 5D1D, 5D1C, 5DC8, 5D1B, 5DC5, 5DC6, 5BWZ
Identifiers
Aliases	HDAC8 , CDLS5, HD8, HDACL1, MRXS6, RPD3, WTS, CDA07, histone deacetylase 8, KDAC8
External IDs	OMIM: 300269; MGI: 1917565; HomoloGene: 41274; GeneCards: HDAC8; OMA:HDAC8 - orthologs
Gene location (Human) Chr. X chromosome (human) [1] Band Xq13.1 Start 72,329,516 bp [1] End 72,573,101 bp [1]
Gene location (Mouse) Chr. X chromosome (mouse) [2] Band X|X D Start 101,328,245 bp [2] End 101,548,965 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in epithelium of colon left adrenal gland left adrenal cortex right adrenal gland tendon of biceps brachii right adrenal cortex gonad Achilles tendon cerebellar hemisphere anterior pituitary Top expressed in wall of esophagus mucosa of esophagus epithelium of esophagus ventricular zone Rathke's pouch dentate gyrus of hippocampal formation granule cell lumbar subsegment of spinal cord right kidney zygote embryo More reference expression data BioGPS n/a
Gene ontology Molecular function Hsp90 protein binding NAD-dependent histone deacetylase activity (H3-K14 specific) histone deacetylase activity metal ion binding Hsp70 protein binding protein binding hydrolase activity chromatin binding transcription factor binding deacetylase activity Cellular component cytoplasm histone deacetylase complex cytosol plasma membrane nucleoplasm nuclear chromosome nucleus Biological process histone H3 deacetylation regulation of transcription, DNA-templated regulation of protein stability regulation of telomere maintenance negative regulation of transcription by RNA polymerase II transcription, DNA-templated sister chromatid cohesion regulation of cohesin loading negative regulation of protein ubiquitination histone deacetylation negative regulation of gene expression cellular response to trichostatin A negative regulation of osteoblast differentiation cellular response to forskolin negative regulation of histone H3-K9 acetylation chromatin organization positive regulation of transcription by RNA polymerase II histone H4 deacetylation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 55869 70315 Ensembl ENSG00000147099 ENSMUSG00000067567 UniProt Q9BY41 Q8VH37 RefSeq (mRNA) NM_001166418 NM_001166419 NM_001166420 NM_001166422 NM_001166448 NM_018486 NM_027382 NM_001313742 RefSeq (protein) NP_001159890 NP_001159891 NP_001159892 NP_001159894 NP_001159920 NP_060956 NP_001300671 NP_081658 Location (UCSC) Chr X: 72.33 – 72.57 Mb Chr X: 101.33 – 101.55 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Histone deacetylase 8 is an enzyme that in humans is encoded by the HDAC8 gene. ^{[5] [6] [7]}

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. ^[7]

Histone deacetylase 8 is involved in skull morphogenesis ^[8] and metabolic control of the ERR-alpha / PGC1-alpha transcriptional complex. ^[9]

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. ^[10] Inhibition of HDAC8 induced apoptosis has been observed in T cell lymphomas. ^[11] In addition the HDAC8 enzyme has been implicated in the pathogenesis of neuroblastoma. ^[12] Therefore, there has been interest in developing HDAC8 selective inhibitors. ^{[13] [14]} At least 20 disease-causing mutations in this gene have been discovered. ^[15]

Interactions

• ERR-alpha. ^[9]

See also

• Histone deacetylase

References

1. GRCh38: Ensembl release 89: ENSG00000147099 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000067567 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. 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. Bibcode:2000FEBSL.478...77V. doi: 10.1016/S0014-5793(00)01813-5 . PMID   10922473. S2CID   12335886.
7. "Entrez Gene: HDAC8 histone deacetylase 8".
8. 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.
9. 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.
10. 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. S2CID   30268983.
11. 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.
12. 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.
13. 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.
14. 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.
15. Šimčíková D, Heneberg P (December 2019). "Refinement of evolutionary medicine predictions based on clinical evidence for the manifestations of Mendelian diseases". Scientific Reports. 9 (1) 18577. Bibcode:2019NatSR...918577S. doi:10.1038/s41598-019-54976-4. PMC   6901466 . PMID   31819097.

Further reading

• Waltregny D, De Leval L, Glénisson W, Ly Tran S, North BJ, Bellahcène A, Weidle U, Verdin E, Castronovo V (2004). "Expression of histone deacetylase 8, a class I histone deacetylase, is restricted to cells showing smooth muscle differentiation in normal human tissues". Am J Pathol. 165 (2): 553–64. doi:10.1016/S0002-9440(10)63320-2. PMC   1618574 . PMID   15277229.
• Glénisson W, Waltregny D, Tran SL, North BJ, Verdin E, Colige A, Castronovo V (June 2005). "Histone deacetylase HDAC8 associates with smooth muscle alpha-actin and is essential for smooth muscle cell contractility". FASEB J. 19 (8): 966–8. doi: 10.1096/fj.04-2303fje . PMID   15772115. S2CID   12006005.
• Wedel T, Van Eys GJ, Waltregny D, Glénisson W, Castronovo V, Vanderwinden JM (2006). "Novel smooth muscle markers reveal abnormalities of the intestinal musculature in severe colorectal motility disorders". Neurogastroenterol. Motil. 18 (7): 526–38. doi:10.1111/j.1365-2982.2006.00781.x. PMID   16771768. S2CID   58462.
• Verdin E, Dequiedt F, Kasler HG (2003). "Class II histone deacetylases: versatile regulators". Trends Genet. 19 (5): 286–93. CiteSeerX   10.1.1.464.415 . doi:10.1016/S0168-9525(03)00073-8. PMID   12711221.
• Hu E, Chen Z, Fredrickson T, et al. (2000). "Cloning and characterization of a novel human class I histone deacetylase that functions as a transcription repressor". J. Biol. Chem. 275 (20): 15254–64. doi: 10.1074/jbc.M908988199 . PMID   10748112.
• Buggy JJ, Sideris ML, Mak P, et al. (2001). "Cloning and characterization of a novel human histone deacetylase, HDAC8". Biochem. J. 350 (1): 199–205. doi:10.1042/0264-6021:3500199. PMC   1221242 . PMID   10926844.
• Amann JM, Nip J, Strom DK, et al. (2001). "ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain". Mol. Cell. Biol. 21 (19): 6470–83. doi:10.1128/MCB.21.19.6470-6483.2001. PMC   99794 . PMID   11533236.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Durst KL, Lutterbach B, Kummalue T, et al. (2003). "The inv(16) fusion protein associates with corepressors via a smooth muscle myosin heavy-chain domain". Mol. Cell. Biol. 23 (2): 607–19. doi:10.1128/MCB.23.2.607-619.2003. PMC   151524 . PMID   12509458.
• Rodriguez M, Yu X, Chen J, Songyang Z (2004). "Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains". J. Biol. Chem. 278 (52): 52914–8. doi: 10.1074/jbc.C300407200 . PMID   14578343.
• Johnson JM, Castle J, Garrett-Engele P, et al. (2004). "Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays". Science. 302 (5653): 2141–4. CiteSeerX   10.1.1.1017.9438 . doi:10.1126/science.1090100. PMID   14684825. S2CID   10007258.
• Lee H, Rezai-Zadeh N, Seto E (2004). "Negative regulation of histone deacetylase 8 activity by cyclic AMP-dependent protein kinase A". Mol. Cell. Biol. 24 (2): 765–73. doi:10.1128/MCB.24.2.765-773.2004. PMC   343812 . PMID   14701748.
• Vannini A, Volpari C, Filocamo G, et al. (2004). "Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor". Proc. Natl. Acad. Sci. U.S.A. 101 (42): 15064–9. Bibcode:2004PNAS..10115064V. doi: 10.1073/pnas.0404603101 . PMC   524051 . PMID   15477595.
• Waltregny D, North B, Van Mellaert F, et al. (2005). "Screening of histone deacetylases (HDAC) expression in human prostate cancer reveals distinct class I HDAC profiles between epithelial and stromal cells". European Journal of Histochemistry. 48 (3): 273–90. PMID   15590418.
• Waltregny D, Glénisson W, Tran SL, et al. (2006). "Histone deacetylase HDAC8 associates with smooth muscle alpha-actin and is essential for smooth muscle cell contractility". FASEB J. 19 (8): 966–8. doi: 10.1096/fj.04-2303fje . PMID   15772115. S2CID   12006005.
• Gantt SL, Gattis SG, Fierke CA (2006). "Catalytic activity and inhibition of human histone deacetylase 8 is dependent on the identity of the active site metal ion". Biochemistry. 45 (19): 6170–8. doi:10.1021/bi060212u. PMID   16681389.
• Lee H, Sengupta N, Villagra A, et al. (2006). "Histone deacetylase 8 safeguards the human ever-shorter telomeres 1B (hEST1B) protein from ubiquitin-mediated degradation". Mol. Cell. Biol. 26 (14): 5259–69. doi:10.1128/MCB.01971-05. PMC   1592721 . PMID   16809764.
• Vannini A, Volpari C, Gallinari P, et al. (2007). "Substrate binding to histone deacetylases as shown by the crystal structure of the HDAC8-substrate complex". EMBO Reports. 8 (9): 879–84. doi:10.1038/sj.embor.7401047. PMC   1973954 . PMID   17721440.
• Nakagawa M, Oda Y, Eguchi T, et al. (2007). "Expression profile of class I histone deacetylases in human cancer tissues". Oncol. Rep. 18 (4): 769–74. doi: 10.3892/or.18.4.769 . PMID   17786334.

External links

• HDAC8+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.