HDAC6
Protein-coding gene in the species Homo sapiens From Wikipedia, the free encyclopedia
Histone deacetylase 6 is an enzyme that in humans is encoded by the HDAC6 gene.[5][6] HDAC6 has emerged as a highly promising candidate to selectively inhibit as a therapeutic strategy to combat several types of cancer and neurodegenerative disorders.[7]
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.[8]
It retracts the cilium of the cell, which is necessary prior to mitosis. [9]
HDAC encourages cell motility and catalyzes α-tubulin deacetylation.[10] As a result the enzyme encourages cancer cell metastasis.[11]
HDAC6 affects transcription and translation by regulating heat-shock protein 90 (Hsp90).
HDAC6 is required in the formation of stress granule (SG) proteins and is instrumental in SG formation; pharmacological inhibition or genetic removal of HDAC6 abolished SG formation.[11]
HDAC6 bonds with high affinity to ubiquitinated proteins.[12]
Clinical relevance
Mutations in this gene have been associated to Alzheimer's disease.[15]
Over expression of this protein correlates with tumorigenesis and cell survival. HDAC6 also encourages metastasis of cancer cells.[11]
Since HDAC6 is dysregulated and/or implicated in several cancers and neurodegenerative disorders, pharmacological inhibition of this specific enzyme holds great therapeutic potential and could also limit side effects associated with pan-inhibitors of multiple HDAC enzymes.[7] Selective inhibition of HDAC6 as a strategy to treat cancers is however also subject of debate, since some HDAC6 inhibitors exhibited anti-tumor activity in vitro and in vivo only when administered in high concentrations, which also produced off-target effects. The findings suggest that further study is needed to clarify data on anti-cancer effects of selective HDAC6 inhibitors.[16]
Interactions
HDAC6 has been shown to interact with HDAC11[17] and Zinc finger and BTB domain-containing protein 16.[18]
HDAC6 interacts with SG (Stress granule) protein G3BP1.[12]
See also
References
Further reading
External links
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