HDAC6

Histone deacetylase 6

Rendering based on PDB 3C5K.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols HDAC6 ; CPBHM; HD6; JM21; PPP1R90
External IDs OMIM: 300272 MGI: 1333752 HomoloGene: 31353 ChEMBL: 1865 GeneCards: HDAC6 Gene
EC number 3.5.1.98
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 10013 15185
Ensembl ENSG00000094631 ENSMUSG00000031161
UniProt Q9UBN7 Q9Z2V5
RefSeq (mRNA) NM_006044 NM_001130416
RefSeq (protein) NP_006035 NP_001123888
Location (UCSC) Chr X:
48.8 – 48.82 Mb
Chr X:
7.93 – 7.95 Mb
PubMed search

Histone deacetylase 6 is an enzyme that in humans is encoded by the HDAC6 gene.[1][2]

Function

Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromatin structure and affects transcription. The protein encoded by this gene belongs to class II of the histone deacetylase/acuc/apha family. It contains an internal duplication of two catalytic domains that appear to function independently of each other. This protein possesses histone deacetylase activity and represses transcription.[3]

Clinical relevance

Mutations in this gene have been associated to Alzheimer's disease.[4]

Over expression of this protein correlates with tumorigenesis and cell survival, HDAC6 also encourages metastasis of cancer cells.[5]

Functions

Retracts the Cilium of the cell, which is necessary prior to mitosis of the cell.[6]

HDAC also encourages cell motility and catalyzes α-tubulin deacetylation.[7] as a result the enzyme also encourages cancer cell metastasis.[5]
HDAC6 also affects transcription and translation by regulating the heat-shock protein 90 (Hsp90) and stress granules (SGs), respectively.[5]

HDAC6 is also known to bond with high affinity to ubiquitinated proteins.[8] HDAC6 is also required in the formation of SG (Stress granule proteins and is instrumental in SG formation; pharmacological inhibition or genetic removal of HDAC6 abolished SG formation.

Interactions

HDAC6 has been shown to interact with HDAC11[9] and Zinc finger and BTB domain-containing protein 16.[10]

HDAC6 interacts with SG (Stress granule) protein G3BP1.[8]

See also

References

  1. Grozinger CM, Hassig CA, Schreiber SL (Jun 1999). "Three proteins define a class of human histone deacetylases related to yeast Hda1p". Proc Natl Acad Sci U S A 96 (9): 4868–73. doi:10.1073/pnas.96.9.4868. PMC 21783. PMID 10220385.
  2. Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (May 1999). "Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res 5 (6): 355–64. doi:10.1093/dnares/5.6.355. PMID 10048485.
  3. "Entrez Gene: HDAC6 histone deacetylase 6".
  4. Cook C, Gendron TF, Scheffel K, Carlomagno Y, Dunmore J, DeTure M, Petrucelli L (5 April 2012). "Loss of HDAC6, a novel CHIP substrate, alleviates abnormal tau accumulation". Human Molecular Genetics. doi:10.1093/hmg/dds125. PMID 22492994.
  5. 1 2 3 Aldana-Masangkay GI, Sakamoto KM (2011). "The role of HDAC6 in cancer". J. Biomed. Biotechnol. 2011: 875824. doi:10.1155/2011/875824. PMC 2975074. PMID 21076528.
  6. Krishnamurthy K, Wang G, Silva J, Condie BG, Bieberich E (February 2007). "Ceramide regulates atypical PKCzeta/lambda-mediated cell polarity in primitive ectoderm cells. A novel function of sphingolipids in morphogenesis". J. Biol. Chem. 282 (5): 3379–90. doi:10.1074/jbc.M607779200. PMID 17105725. Lay summary phys.org/news.
  7. Gao YS, Hubbert CC, Lu J, Lee YS, Lee JY, Yao TP (2007). "Histone deacetylase 6 regulates growth factor-induced actin remodeling and endocytosis". Mol. Cell. Biol. 27 (24): 8637–47. doi:10.1128/MCB.00393-07. PMC 2169396. PMID 17938201.
  8. 1 2 Kwon S, Zhang Y, Matthias P (December 2007). "The deacetylase HDAC6 is a novel critical component of stress granules involved in the stress response". Genes Dev. 21 (24): 3381–94. doi:10.1101/gad.461107. PMC 2113037. PMID 18079183.
  9. Gao L, Cueto MA, Asselbergs F, Atadja P (Jul 2002). "Cloning and functional characterization of HDAC11, a novel member of the human histone deacetylase family". J. Biol. Chem. 277 (28): 25748–55. doi:10.1074/jbc.M111871200. PMID 11948178.
  10. Chauchereau A, Mathieu M, de Saintignon J, Ferreira R, Pritchard LL, Mishal Z, Dejean A, Harel-Bellan A (Nov 2004). "HDAC4 mediates transcriptional repression by the acute promyelocytic leukaemia-associated protein PLZF". Oncogene 23 (54): 8777–84. doi:10.1038/sj.onc.1208128. PMID 15467736.

Further reading

External links

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

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