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Updated: May 11, 2026

Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS
09:20

Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS

Published on: August 10, 2017

A regulatory circuit that involves HR23B and HDAC6 governs the biological response to HDAC inhibitors

M New1, H Olzscha, G Liu

  • 1Laboratory of Cancer Biology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Old Road Campus, off Roosevelt Drive, Headington, Oxford, UK

Cell Death and Differentiation
|May 25, 2013
PubMed

Insights

Histone deacetylase (HDAC) inhibitors affect cancer cell death pathways differently based on HR23B levels. HDAC6 interaction with HR23B, independent of its deacetylase activity, influences whether cells undergo apoptosis or autophagy.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Histone deacetylase (HDAC) inhibitors are emerging anticancer agents.
  • HR23B is a validated biomarker predicting response to HDAC inhibitors.

Purpose of the Study:

  • To elucidate the mechanism by which HR23B influences HDAC inhibitor efficacy.
  • To investigate the interplay between HDAC6, HR23B, and cellular response pathways.

Main Methods:

  • Analysis of HDAC inhibitor effects on cells with varying HR23B expression levels.
  • Investigation of the interaction between HDAC6 and HR23B.
  • Proteomic analysis to identify HDAC6 interactors.

Main Results:

  • HDAC inhibitors induce apoptosis in high HR23B-expressing cells and autophagy in low HR23B-expressing cells.
  • HDAC6 directly downregulates HR23B levels, independent of its deacetylase activity.
  • This downregulation reduces proteasomal degradation of ubiquitinated substrates, desensitizing cells to apoptosis.
  • HSP90 was identified as a key mediator of HDAC6's effect on HR23B.

Conclusions:

  • A novel regulatory mechanism involving HDAC6 and HR23B dictates the cellular response to HDAC inhibitors.
  • This interplay influences whether cancer cells undergo apoptosis or autophagy, impacting therapeutic outcomes.

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