HDAC6

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Protein-coding gene in the species Homo sapiens

title: "HDAC6" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["ec-3.5.1"] description: "Protein-coding gene in the species Homo sapiens" topic_path: "general/ec-3-5-1" source: "https://en.wikipedia.org/wiki/HDAC6" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Protein-coding gene in the species Homo sapiens ::

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

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.

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

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

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.

HDAC6 bonds with high affinity to ubiquitinated proteins.

HDAC6 is involved in leptin sensitivity.

HDAC6 deacetylates threonine residue T178 on TAK1.

Clinical relevance

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

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

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. 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.

Interactions

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

HDAC6 interacts with SG (Stress granule) protein G3BP1.

References

References

  1. (April 1999). "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.
  2. (December 1998). "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.
  3. (May 2022). "Identification of mercaptoacetamide-based HDAC6 inhibitors ''via'' a lean inhibitor strategy: screening, synthesis, and biological evaluation". Chemical Communications.
  4. "Entrez Gene: HDAC6 histone deacetylase 6".
  5. (February 2007). "Ceramide regulates atypical PKCzeta/lambda-mediated cell polarity in primitive ectoderm cells. A novel function of sphingolipids in morphogenesis". The Journal of Biological Chemistry.
  6. (December 2007). "Histone deacetylase 6 regulates growth factor-induced actin remodeling and endocytosis". Molecular and Cellular Biology.
  7. (2011). "The role of HDAC6 in cancer". Journal of Biomedicine & Biotechnology.
  8. (December 2007). "The deacetylase HDAC6 is a novel critical component of stress granules involved in the stress response". Genes & Development.
  9. (2022-01-18). "Targeting an enzyme in fat cells drives rapid weight loss in obese mice".
  10. (October 2022). "HDAC6-dependent deacetylation of TAK1 enhances sIL-6R release to promote macrophage M2 polarization in colon cancer". Cell Death & Disease.
  11. (July 2012). "Loss of HDAC6, a novel CHIP substrate, alleviates abnormal tau accumulation". Human Molecular Genetics.
  12. (August 2019). "Selective pharmacological inhibitors of HDAC6 reveal biochemical activity but functional tolerance in cancer models". International Journal of Cancer.
  13. (July 2002). "Cloning and functional characterization of HDAC11, a novel member of the human histone deacetylase family". The Journal of Biological Chemistry.
  14. (November 2004). "HDAC4 mediates transcriptional repression by the acute promyelocytic leukaemia-associated protein PLZF". Oncogene.

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