Biology:HDAC6

From HandWiki
Short description: Protein-coding gene in the species Homo sapiens

A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Histone deacetylase 6 is an enzyme that in humans is encoded by the HDAC6 gene.[1][2] HDAC6 has emerged as a highly promising candidate to selectively inhibit as a therapeutic strategy to combat several types of cancer and neurodegenerative disorders.[3]

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.[4]

It retracts the cilium of the cell, which is necessary prior to mitosis. [5]

HDAC encourages cell motility and catalyzes α-tubulin deacetylation.[6] As a result, the enzyme encourages cancer cell metastasis.[7]

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.[7]

HDAC6 bonds with high affinity to ubiquitinated proteins.[8]

HDAC6 is involved in leptin sensitivity.[9]

HDAC6 deacetylates tyrosine residue T178 on TAK1.[10]

Clinical relevance

Mutations in this gene have been associated to Alzheimer's disease.[11]

Over expression of this protein correlates with tumorigenesis and cell survival. HDAC6 also encourages metastasis of cancer cells.[7]

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.[3] 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.[12]

Interactions

HDAC6 has been shown to interact with HDAC11[13] and Zinc finger and BTB domain-containing protein 16.[14]

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

See also

References

  1. ↑ "Three proteins define a class of human histone deacetylases related to yeast Hda1p". Proceedings of the National Academy of Sciences of the United States of America 96 (9): 4868–4873. April 1999. doi:10.1073/pnas.96.9.4868. PMID 10220385. Bibcode: 1999PNAS...96.4868G. 
  2. ↑ "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 Research 5 (6): 355–364. December 1998. doi:10.1093/dnares/5.6.355. PMID 10048485. 
  3. ↑ 3.0 3.1 "Identification of mercaptoacetamide-based HDAC6 inhibitors via a lean inhibitor strategy: screening, synthesis, and biological evaluation". Chemical Communications 58 (42): 6239–6242. May 2022. doi:10.1039/D2CC01550A. PMID 35510683. https://biblio.ugent.be/publication/8752799. 
  4. ↑ "Entrez Gene: HDAC6 histone deacetylase 6". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=10013. 
  5. ↑ "Ceramide regulates atypical PKCzeta/lambda-mediated cell polarity in primitive ectoderm cells. A novel function of sphingolipids in morphogenesis". The Journal of Biological Chemistry 282 (5): 3379–3390. February 2007. doi:10.1074/jbc.M607779200. PMID 17105725. *Lay summary in: "Lipid helps cells find their way by keeping their 'antennae' up". July 9, 2012. http://phys.org/news/2012-07-lipid-cells-antennae.html. 
  6. ↑ "Histone deacetylase 6 regulates growth factor-induced actin remodeling and endocytosis". Molecular and Cellular Biology 27 (24): 8637–8647. December 2007. doi:10.1128/MCB.00393-07. PMID 17938201. 
  7. ↑ 7.0 7.1 7.2 "The role of HDAC6 in cancer". Journal of Biomedicine & Biotechnology 2011. 2011. doi:10.1155/2011/875824. PMID 21076528. 
  8. ↑ 8.0 8.1 "The deacetylase HDAC6 is a novel critical component of stress granules involved in the stress response". Genes & Development 21 (24): 3381–3394. December 2007. doi:10.1101/gad.461107. PMID 18079183. 
  9. ↑ "Targeting an enzyme in fat cells drives rapid weight loss in obese mice" (in en-US). 2022-01-18. https://newatlas.com/medical/enzyme-fat-cells-rapid-weight-loss-obese-mice/. 
  10. ↑ "HDAC6-dependent deacetylation of TAK1 enhances sIL-6R release to promote macrophage M2 polarization in colon cancer". Cell Death & Disease 13 (10). October 2022. doi:10.1038/s41419-022-05335-1. PMID 36270986. 
  11. ↑ "Loss of HDAC6, a novel CHIP substrate, alleviates abnormal tau accumulation". Human Molecular Genetics 21 (13): 2936–2945. July 2012. doi:10.1093/hmg/dds125. PMID 22492994. 
  12. ↑ "Selective pharmacological inhibitors of HDAC6 reveal biochemical activity but functional tolerance in cancer models". International Journal of Cancer 145 (3): 735–747. August 2019. doi:10.1002/ijc.32169. PMID 30694564. 
  13. ↑ "Cloning and functional characterization of HDAC11, a novel member of the human histone deacetylase family". The Journal of Biological Chemistry 277 (28): 25748–25755. July 2002. doi:10.1074/jbc.M111871200. PMID 11948178. 
  14. ↑ "HDAC4 mediates transcriptional repression by the acute promyelocytic leukaemia-associated protein PLZF". Oncogene 23 (54): 8777–8784. November 2004. doi:10.1038/sj.onc.1208128. PMID 15467736. 

Further reading

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



Retrieved from "https://handwiki.org/wiki/index.php?title=Biology:HDAC6&oldid=4181516"