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]
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-tubulindeacetylation.[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.
↑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. PMID10048485.
↑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. PMID11948178.
↑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. PMID15467736.
Mahlknecht U, Schnittger S, Landgraf F, Schoch C, Ottmann OG, Hiddemann W, Hoelzer D (2001). "Assignment of the human histone deacetylase 6 gene (HDAC6) to X chromosome p11.23 by in situ hybridization". Cytogenet. Cell Genet. 93 (1–2): 135–6. doi:10.1159/000056967. PMID11474198.
Kao HY, Lee CH, Komarov A, Han CC, Evans RM (2002). "Isolation and characterization of mammalian HDAC10, a novel histone deacetylase". J. Biol. Chem. 277 (1): 187–93. doi:10.1074/jbc.M108931200. PMID11677242.
Gao L, Cueto MA, Asselbergs F, Atadja P (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. PMID11948178.
Hubbert C, Guardiola A, Shao R, Kawaguchi Y, Ito A, Nixon A, Yoshida M, Wang XF, Yao TP (2002). "HDAC6 is a microtubule-associated deacetylase". Nature. 417 (6887): 455–8. doi:10.1038/417455a. PMID12024216.
North BJ, Marshall BL, Borra MT, Denu JM, Verdin E (2003). "The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase". Mol. Cell. 11 (2): 437–44. doi:10.1016/S1097-2765(03)00038-8. PMID12620231.
Voelter-Mahlknecht S, Mahlknecht U (2004). "Cloning and structural characterization of the human histone deacetylase 6 gene". Int. J. Mol. Med. 12 (1): 87–93. doi:10.3892/ijmm.12.1.87. PMID12792815.
Brush MH, Guardiola A, Connor JH, Yao TP, Shenolikar S (2004). "Deactylase inhibitors disrupt cellular complexes containing protein phosphatases and deacetylases". J. Biol. Chem. 279 (9): 7685–91. doi:10.1074/jbc.M310997200. PMID14670976.
Pandey UB, Nie Z, Batlevi Y, McCray BA, Ritson GP, Nedelsky NB, Schwartz SL, DiProspero NA, Knight MA, Schuldiner O, Padmanabhan R, Hild M, Berry DL, Garza D, Hubbert CC, Yao TP, Baehrecke EH, Taylor JP (June 14, 2007). "HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS". Nature. 447 (7146): 859–63. doi:10.1038/nature05853. PMID17568747.