From Wikipedia, the free encyclopedia
Protein-coding gene in the species Homo sapiens
Histone deacetylase 5 is an
enzyme that in humans is encoded by the HDAC5
gene .
[5]
[6]
[7]
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.
[7]
AMP-activated protein kinase regulation of the glucose transporter
GLUT4 occurs by
phosphorylation of HDAC5.
[8]
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.
[9] Its function can be effectively examined by siRNA knockdown based on an independent validation.
[10]
HDAC5 overexpression in
urothelial carcinoma cell lines inhibits long-term proliferation but can promote epithelial-to-mesenchymal transition (
EMT )
[11]
Interactions
Histone deacetylase 5 has been shown to
interact with:
BCL6 ,
[12]
CBX5 ,
[13]
GATA1 ,
[14]
HDAC3 ,
[5]
[15]
[16]
[17]
IKZF1 ,
[18]
MEF2A ,
[19]
NRIP1 ,
[20]
NCOR1 ,
[15]
[21]
NCOR2 ,
[21]
YWHAQ ,
[22] and
ZBTB16 .
[12]
[23]
See also
References
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000108840 –
Ensembl , May 2017
^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000008855 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
a
b Grozinger CM, Hassig CA, Schreiber SL (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 . 96 (9): 4868–73.
Bibcode :
1999PNAS...96.4868G .
doi :
10.1073/pnas.96.9.4868 .
PMC
21783 .
PMID
10220385 .
^ Scanlan MJ, Chen YT, Williamson B, Gure AO, Stockert E, Gordan JD, et al. (May 1998). "Characterization of human colon cancer antigens recognized by autologous antibodies". International Journal of Cancer . 76 (5): 652–8.
doi :
10.1002/(SICI)1097-0215(19980529)76:5<652::AID-IJC7>3.0.CO;2-P .
PMID
9610721 .
S2CID
916155 .
^
a
b
"Entrez Gene: HDAC5 histone deacetylase 5" .
^ McGee SL, van Denderen BJ, Howlett KF, Mollica J, Schertzer JD, Kemp BE, Hargreaves M (April 2008).
"AMP-activated protein kinase regulates GLUT4 transcription by phosphorylating histone deacetylase 5" . Diabetes . 57 (4): 860–7.
doi :
10.2337/db07-0843 .
PMID
18184930 .
S2CID
17274354 .
^ Agis-Balboa RC, Pavelka Z, Kerimoglu C, Fischer A (January 2013). "Loss of HDAC5 impairs memory function: implications for Alzheimer's disease". Journal of Alzheimer's Disease . 33 (1): 35–44.
doi :
10.3233/JAD-2012-121009 .
hdl :
2434/223089 .
PMID
22914591 .
^ Munkácsy G, Sztupinszki Z, Herman P, Bán B, Pénzváltó Z, Szarvas N, Győrffy B (September 2016).
"Validation of RNAi Silencing Efficiency Using Gene Array Data shows 18.5% Failure Rate across 429 Independent Experiments" . Molecular Therapy: Nucleic Acids . 5 (9): e366.
doi :
10.1038/mtna.2016.66 .
PMC
5056990 .
PMID
27673562 .
^ Jaguva Vasudevan AA, Hoffmann MJ, Beck ML, Poschmann G, Petzsch P, Wiek C, et al. (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 . 20 (9): 2135.
doi :
10.3390/ijms20092135 .
PMC
6539474 .
PMID
31052182 .
^
a
b Lemercier C, Brocard MP, Puvion-Dutilleul F, Kao HY, Albagli O, Khochbin S (June 2002).
"Class II histone deacetylases are directly recruited by BCL6 transcriptional repressor" . The Journal of Biological Chemistry . 277 (24): 22045–52.
doi :
10.1074/jbc.M201736200 .
PMID
11929873 .
^ Zhang CL, McKinsey TA, Olson EN (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 . 22 (20): 7302–12.
doi :
10.1128/MCB.22.20.7302-7312.2002 .
PMC
139799 .
PMID
12242305 .
^ Watamoto K, Towatari M, Ozawa Y, Miyata Y, Okamoto M, Abe A, et al. (December 2003). "Altered interaction of HDAC5 with GATA-1 during MEL cell differentiation". Oncogene . 22 (57): 9176–84.
doi :
10.1038/sj.onc.1206902 .
PMID
14668799 .
S2CID
24491249 .
^
a
b Zhang J, Kalkum M, Chait BT, Roeder RG (March 2002).
"The N-CoR-HDAC3 nuclear receptor corepressor complex inhibits the JNK pathway through the integral subunit GPS2" . Molecular Cell . 9 (3): 611–23.
doi :
10.1016/S1097-2765(02)00468-9 .
PMID
11931768 .
^ Fischle W, Dequiedt F, Hendzel MJ, Guenther MG, Lazar MA, Voelter W, Verdin E (January 2002). "Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT/N-CoR". Molecular Cell . 9 (1): 45–57.
doi :
10.1016/S1097-2765(01)00429-4 .
hdl :
11858/00-001M-0000-002C-9FF9-9 .
PMID
11804585 .
^ Grozinger CM, Schreiber SL (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 . 97 (14): 7835–40.
Bibcode :
2000PNAS...97.7835G .
doi :
10.1073/pnas.140199597 .
PMC
16631 .
PMID
10869435 .
^ Koipally J, Georgopoulos K (August 2002).
"A molecular dissection of the repression circuitry of Ikaros" . The Journal of Biological Chemistry . 277 (31): 27697–705.
doi :
10.1074/jbc.M201694200 .
PMID
12015313 .
^ Lemercier C, Verdel A, Galloo B, Curtet S, Brocard MP, Khochbin S (May 2000).
"mHDA1/HDAC5 histone deacetylase interacts with and represses MEF2A transcriptional activity" . The Journal of Biological Chemistry . 275 (20): 15594–9.
doi :
10.1074/jbc.M908437199 .
PMID
10748098 .
^ Castet A, Boulahtouf A, Versini G, Bonnet S, Augereau P, Vignon F, et al. (2004).
"Multiple domains of the Receptor-Interacting Protein 140 contribute to transcription inhibition" . Nucleic Acids Research . 32 (6): 1957–66.
doi :
10.1093/nar/gkh524 .
PMC
390375 .
PMID
15060175 .
^
a
b Huang EY, Zhang J, Miska EA, Guenther MG, Kouzarides T, Lazar MA (January 2000).
"Nuclear receptor corepressors partner with class II histone deacetylases in a Sin3-independent repression pathway" . Genes & Development . 14 (1): 45–54.
doi :
10.1101/gad.14.1.45 .
PMC
316335 .
PMID
10640275 .
^ Vega RB, Harrison BC, Meadows E, Roberts CR, Papst PJ, Olson EN, McKinsey TA (October 2004).
"Protein kinases C and D mediate agonist-dependent cardiac hypertrophy through nuclear export of histone deacetylase 5" . Molecular and Cellular Biology . 24 (19): 8374–85.
doi :
10.1128/MCB.24.19.8374-8385.2004 .
PMC
516754 .
PMID
15367659 .
^ Chauchereau A, Mathieu M, de Saintignon J, Ferreira R, Pritchard LL, Mishal Z, et al. (November 2004). "HDAC4 mediates transcriptional repression by the acute promyelocytic leukaemia-associated protein PLZF". Oncogene . 23 (54): 8777–84.
doi :
10.1038/sj.onc.1208128 .
PMID
15467736 .
S2CID
26092755 .
Further reading
Verdin E, Dequiedt F, Kasler HG (May 2003).
"Class II histone deacetylases: versatile regulators" (PDF) . Trends in Genetics . 19 (5): 286–93.
doi :
10.1016/S0168-9525(03)00073-8 .
hdl :
2268/80861 .
PMID
12711221 .
Huang EY, Zhang J, Miska EA, Guenther MG, Kouzarides T, Lazar MA (January 2000).
"Nuclear receptor corepressors partner with class II histone deacetylases in a Sin3-independent repression pathway" . Genes & Development . 14 (1): 45–54.
doi :
10.1101/gad.14.1.45 .
PMC
316335 .
PMID
10640275 .
Lemercier C, Verdel A, Galloo B, Curtet S, Brocard MP, Khochbin S (May 2000).
"mHDA1/HDAC5 histone deacetylase interacts with and represses MEF2A transcriptional activity" . The Journal of Biological Chemistry . 275 (20): 15594–9.
doi :
10.1074/jbc.M908437199 .
PMID
10748098 .
Grozinger CM, Schreiber SL (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 . 97 (14): 7835–40.
Bibcode :
2000PNAS...97.7835G .
doi :
10.1073/pnas.140199597 .
PMC
16631 .
PMID
10869435 .
Huynh KD, Fischle W, Verdin E, Bardwell VJ (July 2000).
"BCoR, a novel corepressor involved in BCL-6 repression" . Genes & Development . 14 (14): 1810–23.
doi :
10.1101/gad.14.14.1810 .
PMC
316791 .
PMID
10898795 .
Mahlknecht U , Schnittger S, Ottmann OG, Schoch C, Mosebach M, Hiddemann W, Hoelzer D (October 2000). "Chromosomal organization and localization of the human histone deacetylase 5 gene (HDAC5)". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression . 1493 (3): 342–8.
doi :
10.1016/S0167-4781(00)00191-3 .
PMID
11018260 .
Zhang CL, McKinsey TA, Lu JR, Olson EN (January 2001).
"Association of COOH-terminal-binding protein (CtBP) and MEF2-interacting transcription repressor (MITR) contributes to transcriptional repression of the MEF2 transcription factor" . The Journal of Biological Chemistry . 276 (1): 35–9.
doi :
10.1074/jbc.M007364200 .
PMID
11022042 .
McKinsey TA, Zhang CL, Lu J, Olson EN (November 2000).
"Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation" . Nature . 408 (6808): 106–11.
Bibcode :
2000Natur.408..106M .
doi :
10.1038/35040593 .
PMC
4459600 .
PMID
11081517 .
McKinsey TA, Zhang CL, Olson EN (December 2000).
"Activation of the myocyte enhancer factor-2 transcription factor by calcium/calmodulin-dependent protein kinase-stimulated binding of 14-3-3 to histone deacetylase 5" . Proceedings of the National Academy of Sciences of the United States of America . 97 (26): 14400–5.
Bibcode :
2000PNAS...9714400M .
doi :
10.1073/pnas.260501497 .
PMC
18930 .
PMID
11114197 .
Fischle W, Dequiedt F, Fillion M, Hendzel MJ, Voelter W, Verdin E (September 2001).
"Human HDAC7 histone deacetylase activity is associated with HDAC3 in vivo" . The Journal of Biological Chemistry . 276 (38): 35826–35.
doi :
10.1074/jbc.M104935200 .
PMID
11466315 .
McKinsey TA, Zhang CL, Olson EN (September 2001).
"Identification of a signal-responsive nuclear export sequence in class II histone deacetylases" . Molecular and Cellular Biology . 21 (18): 6312–21.
doi :
10.1128/MCB.21.18.6312-6321.2001 .
PMC
87361 .
PMID
11509672 .
Ozawa Y, Towatari M, Tsuzuki S, Hayakawa F, Maeda T, Miyata Y, et al. (October 2001). "Histone deacetylase 3 associates with and represses the transcription factor GATA-2". Blood . 98 (7): 2116–23.
doi :
10.1182/blood.V98.7.2116 .
PMID
11567998 .
Potter GB, Beaudoin GM, DeRenzo CL, Zarach JM, Chen SH, Thompson CC (October 2001).
"The hairless gene mutated in congenital hair loss disorders encodes a novel nuclear receptor corepressor" . Genes & Development . 15 (20): 2687–701.
doi :
10.1101/gad.916701 .
PMC
312820 .
PMID
11641275 .
Fischle W, Dequiedt F, Hendzel MJ, Guenther MG, Lazar MA, Voelter W, Verdin E (January 2002). "Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT/N-CoR". Molecular Cell . 9 (1): 45–57.
doi :
10.1016/S1097-2765(01)00429-4 .
hdl :
11858/00-001M-0000-002C-9FF9-9 .
PMID
11804585 .
Lemercier C, Brocard MP, Puvion-Dutilleul F, Kao HY, Albagli O, Khochbin S (June 2002).
"Class II histone deacetylases are directly recruited by BCL6 transcriptional repressor" . The Journal of Biological Chemistry . 277 (24): 22045–52.
doi :
10.1074/jbc.M201736200 .
PMID
11929873 .
Huang Y, Tan M, Gosink M, Wang KK, Sun Y (May 2002). "Histone deacetylase 5 is not a p53 target gene, but its overexpression inhibits tumor cell growth and induces apoptosis". Cancer Research . 62 (10): 2913–22.
PMID
12019172 .
External links
This article incorporates text from the
United States National Library of Medicine , which is in the
public domain .
Activity Regulation Classification Kinetics Types