Histone deacetylase 5

Function

Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to the class II histone deacetylase/acuc/apha family. It possesses histone deacetylase activity and represses transcription when tethered to a promoter. It coimmunoprecipitates only with HDAC3 family member and might form multicomplex proteins. It also interacts with myocyte enhancer factor-2 (MEF2) proteins, resulting in repression of MEF2-dependent genes. This gene is thought to be associated with colon cancer. Two transcript variants encoding different isoforms have been found for this gene.

AMP-activated protein kinase regulation of the glucose transporter GLUT4 occurs by phosphorylation of HDAC5.

HDAC5 is involved in memory consolidation and suggests that development of more selective HDAC inhibitors for the treatment of Alzheimer's disease should avoid targeting HDAC5. Its function can be effectively examined by siRNA knockdown based on an independent validation.

HDAC5 overexpression in urothelial carcinoma cell lines inhibits long-term proliferation but can promote epithelial-to-mesenchymal transition (EMT)

Interactions

Histone deacetylase 5 has been shown to interact with:

• BCL6,
• CBX5,
• GATA1,
• HDAC3,
• IKZF1,
• MEF2A,
• NRIP1,
• NCOR1,
• NCOR2,
• YWHAQ, and
• ZBTB16.

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. (May 1998). "Characterization of human colon cancer antigens recognized by autologous antibodies". International Journal of Cancer.
3. "Entrez Gene: HDAC5 histone deacetylase 5".
4. (April 2008). "AMP-activated protein kinase regulates GLUT4 transcription by phosphorylating histone deacetylase 5". Diabetes.
5. (January 2013). "Loss of HDAC5 impairs memory function: implications for Alzheimer's disease". Journal of Alzheimer's Disease.
6. (September 2016). "Validation of RNAi Silencing Efficiency Using Gene Array Data shows 18.5% Failure Rate across 429 Independent Experiments". Molecular Therapy: Nucleic Acids.
7. (April 2019). "HDAC5 Expression in Urothelial Carcinoma Cell Lines Inhibits Long-Term Proliferation but Can Promote Epithelial-to-Mesenchymal Transition". International Journal of Molecular Sciences.
8. (October 2002). "Association of class II histone deacetylases with heterochromatin protein 1: potential role for histone methylation in control of muscle differentiation". Molecular and Cellular Biology.
9. (December 2003). "Altered interaction of HDAC5 with GATA-1 during MEL cell differentiation". Oncogene.
10. (January 2002). "Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT/N-CoR". Molecular Cell.
11. (July 2000). "Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization". Proceedings of the National Academy of Sciences of the United States of America.
12. (August 2002). "A molecular dissection of the repression circuitry of Ikaros". The Journal of Biological Chemistry.
13. (May 2000). "mHDA1/HDAC5 histone deacetylase interacts with and represses MEF2A transcriptional activity". The Journal of Biological Chemistry.
14. (2004). "Multiple domains of the Receptor-Interacting Protein 140 contribute to transcription inhibition". Nucleic Acids Research.
15. (March 2002). "The N-CoR-HDAC3 nuclear receptor corepressor complex inhibits the JNK pathway through the integral subunit GPS2". Molecular Cell.
16. (January 2000). "Nuclear receptor corepressors partner with class II histone deacetylases in a Sin3-independent repression pathway". Genes & Development.
17. (October 2004). "Protein kinases C and D mediate agonist-dependent cardiac hypertrophy through nuclear export of histone deacetylase 5". Molecular and Cellular Biology.
18. (June 2002). "Class II histone deacetylases are directly recruited by BCL6 transcriptional repressor". The Journal of Biological Chemistry.
19. (November 2004). "HDAC4 mediates transcriptional repression by the acute promyelocytic leukaemia-associated protein PLZF". Oncogene.