Histone Deacetylase Inhibitors (HDACi) Cause the Selective Depletion of Bromodomain Containing Proteins (BCPs).

Molecular & Cellular Proteomics : MCP
Marie-Therese MackmullMartin Beck

Abstract

Histone deacetylases (HDACs) and acetyltransferases control the epigenetic regulation of gene expression through modification of histone marks. Histone deacetylase inhibitors (HDACi) are small molecules that interfere with histone tail modification, thus altering chromatin structure and epigenetically controlled pathways. They promote apoptosis in proliferating cells and are promising anticancer drugs. While some HDACi have already been approved for therapy and others are in different phases of clinical trials, the exact mechanism of action of this drug class remains elusive. Previous studies have shown that HDACis cause massive changes in chromatin structure but only moderate changes in gene expression. To what extent these changes manifest at the protein level has never been investigated on a proteome-wide scale. Here, we have studied HDACi-treated cells by large-scale mass spectrometry based proteomics. We show that HDACi treatment affects primarily the nuclear proteome and induces a selective decrease of bromodomain-containing proteins (BCPs), the main readers of acetylated histone marks. By combining time-resolved proteome and transcriptome profiling, we show that BCPs are affected at the protein level as early as 12 h aft...Continue Reading

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Citations

Oct 16, 2016·Applied Microbiology and Biotechnology·Salwa Mansur AliNaveed Ahmed Khan
Jan 25, 2018·Molecular & Cellular Proteomics : MCP·Katarzyna BuczakMartin Beck
Oct 28, 2017·Molecular Biology of the Cell·Mathieu GendarmeJan H Reiling
Dec 20, 2017·Molecular Systems Biology·Marie-Therese MackmullMartin Beck
Apr 1, 2020·International Journal of Molecular Sciences·Barbara WójcikowskaMałgorzata D Gaj
Sep 13, 2017·Expert Review of Proteomics·Cassandra G EubanksMichael P Washburn
Jun 16, 2017·Epigenomics·Thea van den BoschFrank J Dekker
Aug 17, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sangiliyandi GurunathanJin-Hoi Kim
Jul 28, 2020·International Journal of Molecular Sciences·Liang YuLin Gao
Jul 26, 2018·Scientific Reports·Kerstin KleinCaroline Ospelt

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Datasets Mentioned

BETA
PXD001660
GSE64689

Methods Mentioned

BETA
acetylation
PCR
histone acetylation
PBAF

Software Mentioned

Bioconductor
R package “ drc
MaxQuant
ImmuQuest
limma
Andromeda
Affymetrix Tools
R

Related Concepts

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The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

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