Inhibition of androgen receptor activity by histone deacetylase 4 through receptor SUMOylation

Yang, Y; Tse, A K-W; Li, P; Ma, Q; Xiang, S; Nicosia, S V; Seto, E; Zhang, X; Bai, W

doi:10.1038/onc.2010.600

Cited by 73Prostate Cancer Treatment and ResearchHistone Deacetylase Inhibitors ResearchUbiquitin and proteasome pathways

Inhibition of androgen receptor activity by histone deacetylase 4 through receptor SUMOylation

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Yang, Y, Tse, A K-W, Li, P, Ma, Q, Xiang, S, Nicosia, S V, Seto, E, Zhang, X +1 more·2011·Oncogene

DOI 10.1038/onc.2010.600PMC PMC3093431

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Abstract

The transcriptional activity of the androgen receptor (AR) is regulated by both ligand binding and post-translational modifications, including acetylation and small ubiquitin-like modifier (SUMO)ylation. Histone deacetylases (HDACs) are known to catalyze the removal of acetyl groups from both histones and non-histone proteins. In this study, we report that HDAC4 binds to and inhibits the activity of the AR. This inhibition was found to depend on the SUMOylation, instead of deacetylation, of the AR. Consistently, HDAC4 increases the level of AR SUMOylation in both whole-cell and cell-free assay systems, raising the possibility that the deacetylase may act as an E3 ligase for AR SUMOylation. Knock down of HDAC4 increases the activity of endogenous AR and androgen induction of prostate-specific antigen expression and prostate cancer cell growth, which is associated with decreased SUMOylation of the receptor. Overall, the studies identify HDAC4 as a positive regulator for AR SUMOylation, revealing a deacetylase-independent mechanism of HDAC action in prostate cancer cells.

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HDAC4 belongs to the SUMO E3 ligase family and can directly SUMOylate IκBα, AR, LXRα, and MEF2.
“Additionally, HDAC4 belongs to the SUMO E3 ligase family and can directly SUMOylate IκBα, AR, LXRα, and MEF217–20.”
From An HDAC4-specific PROTAC degrader achieves radiation sensitization by enhancing ferroptosis in lung cancer (2026) · cites this paper as [20]
The Results section reports that HDAC4 increases AR SUMOylation. The Discussion describes HDAC4 as a *possible* SUMO E3 ligase, notes reports concerning MEF2 and LXR, and says AR SUMOylation might instead be enhanced through other E3 enzymes. It does not establish direct SUMOylation of all four named proteins, and the searched passages do not address IκBα. Page numbers were not supplied. (LLM, conf=0.88)
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Inhibition of androgen receptor activity by histone deacetylase 4 through receptor SUMOylation. Oncogene 2011
Yang, Y., Tse, A., Li, P., Ma, Q., Xiang, S., Nicosia, S. V., Seto, E., Zhang, X. M., & Bai, W. (2016)
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Histone Deacetylases Are Required for Androgen Receptor Function in Hormone-Sensitive and Castrate-Resistant Prostate Cancer
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Authors: Yang, Y., Tse, A. K.-W., Li, P., Ma, Q., Xiang, S., Nicosia, S. V., Seto, E., Zhang, X., & Bai, W.
Affiliations: University of South Florida (US)
Corresponding author: Bai, W
ORCID: Yang, Y
Tse, A K-W
Li, P
Xiang, S
Seto, E
Bai, W
Venue: Oncogene
Publisher: Springer Science and Business Media LLC
Published: 2011-01-17
Volume: 30
Issue: 19
Pages: 2207-2218
ISSN: 0950-9232 (ISSN-L)
1476-5594
DOI: 10.1038/onc.2010.600
PMC: PMC3093431
OpenAlex: W1980337598
Cited by: 72
References: 39
Citations by year: 2026: 1 · 2025: 2 · 2024: 6 · 2023: 1 · 2022: 6 · 2021: 7 · 2020: 2 · 2019: 3 · 2018: 1 · 2017: 2 · 2016: 7 · 2015: 4 · 2014: 5 · 2013: 12 · 2012: 8
FWCI: 7.77
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Oncogene (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (CA111334, R01CA093666, R01CA111334, CA93666)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
Keywords: androgen receptor, HDAC4, SUMOylation, E3 ubiquitin ligase, transcriptional repression, prostate cancer, prostate-specific antigen, androgen induction, post-translational modification
MeSH terms: Androgen Antagonists, Base Sequence, Enzyme-Linked Immunosorbent Assay, Histone Deacetylases, Humans, Receptors, Androgen, Repressor Proteins, Signal Transduction, DNA Primers, Cell Line, Tumor, Biocatalysis, Sumoylation

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Inhibition of androgen receptor activity by histone deacetylase 4 through receptor SUMOylation

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