HDAC8

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Histone deacetylase 8
Protein HDAC8 PDB 1t64.png
PDB rendering based on 1t64.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols HDAC8 ; CDLS5; HD8; HDACL1; MRXS6; RPD3; WTS
External IDs OMIM300269 MGI1917565 HomoloGene41274 ChEMBL: 3192 GeneCards: HDAC8 Gene
EC number 3.5.1.98
Orthologs
Species Human Mouse
Entrez 55869 70315
Ensembl ENSG00000147099 ENSMUSG00000067567
UniProt Q9BY41 Q8VH37
RefSeq (mRNA) NM_001166418 NM_027382
RefSeq (protein) NP_001159890 NP_081658
Location (UCSC) Chr HG1438_PATCH:
71.55 – 71.79 Mb
Chr X:
102.28 – 102.51 Mb
PubMed search [1] [2]

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

Function[edit]

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[edit]

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[edit]

See also[edit]


References[edit]

  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. ^ a b "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. ^ a b 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. 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. 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[edit]

External links[edit]

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