Related Experiment Video

Updated: Jun 26, 2026

Assays for Validating Histone Acetyltransferase Inhibitors
09:11

Assays for Validating Histone Acetyltransferase Inhibitors

Published on: August 6, 2020

Histone deacetylases are required for androgen receptor function in hormone-sensitive and castrate-resistant prostate

Derek S Welsbie1, Jin Xu, Yu Chen

  • 1David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA.

Cancer Research
|January 30, 2009
PubMed

Insights

Histone deacetylase (HDAC) inhibitors suppress androgen receptor (AR) activity in prostate cancer, offering a potential therapy when hormone treatments fail. These inhibitors block AR-driven gene expression by preventing essential complex assembly, even in resistant cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Androgen receptor (AR) transcriptional activity drives prostate cancer growth, persisting even with resistance to standard therapies.
  • Novel therapeutic strategies are required to suppress AR activity when conventional hormone treatments are ineffective.

Purpose of the Study:

  • To investigate the potential of histone deacetylase (HDAC) inhibitors as a therapeutic approach for prostate cancer, particularly in cases of therapy resistance.
  • To elucidate the mechanism by which HDAC inhibitors suppress AR transcriptional activity.

Main Methods:

  • Treatment of prostate cancer cells with HDAC inhibitors (SAHA, LBH589) and genetic knockdown of HDAC1/HDAC3.
  • Analysis of AR-mediated gene expression, including the TMPRSS2 gene.
  • Assessment of AR protein levels and the assembly of coactivator/RNA polymerase II complexes.
  • Evaluation of HDAC inhibitor efficacy in castration-resistant prostate cancer models.

Main Results:

  • HDAC inhibitors effectively block AR-mediated transcriptional activation of target genes, including TMPRSS2.
  • Genetic depletion of HDAC1 or HDAC3 mimics the suppressive effects of HDAC inhibitors on AR-regulated genes.
  • HDAC inhibitors inhibit AR activity by disrupting coactivator/RNA polymerase II complex assembly at gene enhancers, independent of AR protein levels.
  • This disruption is linked to altered AR recruitment dynamics.
  • HDAC inhibitors demonstrate efficacy in castration-resistant prostate cancer models.

Conclusions:

  • HDAC inhibitors represent a promising therapeutic strategy for prostate cancer, especially in castration-resistant settings.
  • HDAC inhibitors function by inhibiting the assembly of transcriptional machinery required for AR activity.
  • Defined HDAC-regulated AR target genes can serve as biomarkers for monitoring HDAC inhibition efficacy.

More Related Videos

Murine Prostate Micro-dissection and Surgical Castration08:49

Murine Prostate Micro-dissection and Surgical Castration

Published on: May 11, 2016

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel06:44

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel

Published on: September 8, 2017

Related Concept Videos

Spreading of Chromatin Modifications02:25

Spreading of Chromatin Modifications

The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer is an enzyme that can...
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Histone Modification02:32

Histone Modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Histone Modification02:32

Histone Modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...