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@article{2253735,
author = {Zrimsek, Masa and Kuchaříková, Hana and Draganic, Kristina and Pírek, Pavlína and Spornberger, Verena Heiss and Winkelmayer, Lisa and Hassler, Melanie R and Lochmanová, Gabriela and Zdráhal, Zbyněk and Egger, Gerda},
article_number = {15},
doi = {http://dx.doi.org/10.3390/cells11152380},
keywords = {histone deacetylases; histone deacetylase inhibitors; SAHA; vorinostat; MS-275; entinostat; proteomics; acetylomics; anaplastic large cell lymphoma; ALCL},
language = {eng},
issn = {2073-4409},
journal = {CELLS},
title = {Quantitative Acetylomics Uncover Acetylation-Mediated Pathway Changes Following Histone Deacetylase Inhibition in Anaplastic Large Cell Lymphoma},
url = {https://www.mdpi.com/2073-4409/11/15/2380},
volume = {11},
year = {2022}
}
TY - JOUR
ID - 2253735
AU - Zrimsek, Masa - Kuchaříková, Hana - Draganic, Kristina - Pírek, Pavlína - Spornberger, Verena Heiss - Winkelmayer, Lisa - Hassler, Melanie R - Lochmanová, Gabriela - Zdráhal, Zbyněk - Egger, Gerda
PY - 2022
TI - Quantitative Acetylomics Uncover Acetylation-Mediated Pathway Changes Following Histone Deacetylase Inhibition in Anaplastic Large Cell Lymphoma
JF - CELLS
VL - 11
IS - 15
SP - 2380
EP - 2380
PB - MDPI
SN - 20734409
KW - histone deacetylases
KW - histone deacetylase inhibitors
KW - SAHA
KW - vorinostat
KW - MS-275
KW - entinostat
KW - proteomics
KW - acetylomics
KW - anaplastic large cell lymphoma
KW - ALCL
UR - https://www.mdpi.com/2073-4409/11/15/2380
N2 - Histone deacetylases (HDACs) target acetylated lysine residues in histone and non-histone proteins. HDACs are implicated in the regulation of genomic stability, cell cycle, cell death and differentiation and thus critically involved in tumorigenesis. Further, HDACs regulate T-cell development and HDAC inhibitors (HDACis) have been approved for clinical use in some T-cell malignancies. Still, the exact targets and mechanisms of HDAC inhibition in cancer are understudied. We isolated tumor cell lines from a transgenic mouse model of anaplastic large cell lymphoma (ALCL), a rare T-cell lymphoma, and abrogated HDAC activity by treatment with the HDACis Vorinostat and Entinostat or Cre-mediated deletion of Hdac1. Changes in overall protein expression as well as histone and protein acetylation were measured following Hdac1 deletion or pharmacological inhibition using label-free liquid chromatography mass spectrometry (LC-MS/MS). We found changes in overall protein abundance and increased acetylation of histones and non-histone proteins, many of which were newly discovered and associated with major metabolic and DNA damage pathways. For non-histone acetylation, we mapped a total of 1204 acetylated peptides corresponding to 603 proteins, including chromatin modifying proteins and transcription factors. Hyperacetylated proteins were involved in processes such as transcription, RNA metabolism and DNA damage repair (DDR). The DDR pathway was majorly affected by hyperacetylation following HDAC inhibition. This included acetylation of H2AX, PARP1 and previously unrecognized acetylation sites in TP53BP1. Our data provide a comprehensive view of the targets of HDAC inhibition in malignant T cells with general applicability and could have translational impact for the treatment of ALCL with HDACis alone or in combination therapies.
ER -
ZRIMSEK, Masa, Hana KUCHAŘÍKOVÁ, Kristina DRAGANIC, Pavlína PÍREK, Verena Heiss SPORNBERGER, Lisa WINKELMAYER, Melanie R HASSLER, Gabriela LOCHMANOVÁ, Zbyněk ZDRÁHAL a Gerda EGGER. Quantitative Acetylomics Uncover Acetylation-Mediated Pathway Changes Following Histone Deacetylase Inhibition in Anaplastic Large Cell Lymphoma. \textit{CELLS}. MDPI, 2022, roč.~11, č.~15, s.~2380-2402. ISSN~2073-4409. Dostupné z: https://dx.doi.org/10.3390/cells11152380.
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