Quantitative Acetylomics Uncover Acetylation-Mediated Pathway
Changes Following Histone Deacetylase Inhibition in Anaplastic
Large Cell Lymphoma

J 2022

Quantitative Acetylomics Uncover Acetylation-Mediated Pathway Changes Following Histone Deacetylase Inhibition in Anaplastic Large Cell Lymphoma

ZRIMSEK, Masa, Hana KUCHAŘÍKOVÁ, Kristina DRAGANIC, Pavlína PÍREK, Verena Heiss SPORNBERGER et. al.

Basic information

Original name

Quantitative Acetylomics Uncover Acetylation-Mediated Pathway Changes Following Histone Deacetylase Inhibition in Anaplastic Large Cell Lymphoma

Authors

ZRIMSEK, Masa, Hana KUCHAŘÍKOVÁ (203 Czech Republic, belonging to the institution), Kristina DRAGANIC, Pavlína PÍREK (203 Czech Republic, belonging to the institution), Verena Heiss SPORNBERGER, Lisa WINKELMAYER, Melanie R HASSLER, Gabriela LOCHMANOVÁ (203 Czech Republic, belonging to the institution), Zbyněk ZDRÁHAL (203 Czech Republic, guarantor, belonging to the institution) and Gerda EGGER

Edition

CELLS, MDPI, 2022, 2073-4409

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10601 Cell biology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 6.000

RIV identification code

RIV/00216224:14740/22:00128595

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.3390/cells11152380

UT WoS

000839344600001

Keywords in English

histone deacetylases; histone deacetylase inhibitors; SAHA; vorinostat; MS-275; entinostat; proteomics; acetylomics; anaplastic large cell lymphoma; ALCL

Abstract

V originále

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.

Links

EF18_046/0015974, research and development project

Name: Modernizace České infrastruktury pro integrativní strukturní biologii

GF19-29701L, research and development project

Name: Funkce HDAC1 v T-buněčných lymfomech

Investor: Czech Science Foundation, Partner Agency (Austria)

LM2018140, research and development project

Name: e-Infrastruktura CZ (Acronym: e-INFRA CZ)

Investor: Ministry of Education, Youth and Sports of the CR

90127, large research infrastructures

Name: CIISB II

Citovat

ZRIMSEK, Masa, Hana KUCHAŘÍKOVÁ, Kristina DRAGANIC, Pavlína PÍREK, Verena Heiss SPORNBERGER, Lisa WINKELMAYER, Melanie R HASSLER, Gabriela LOCHMANOVÁ, Zbyněk ZDRÁHAL and Gerda EGGER. Quantitative Acetylomics Uncover Acetylation-Mediated Pathway Changes Following Histone Deacetylase Inhibition in Anaplastic Large Cell Lymphoma. CELLS. MDPI, 2022, vol. 11, No 15, p. 2380-2402. ISSN 2073-4409. Available from: https://dx.doi.org/10.3390/cells11152380.

@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 and Gerda EGGER. Quantitative Acetylomics Uncover Acetylation-Mediated Pathway Changes Following Histone Deacetylase Inhibition in Anaplastic Large Cell Lymphoma. \textit{CELLS}. MDPI, 2022, vol.~11, No~15, p.~2380-2402. ISSN~2073-4409. Available from: https://dx.doi.org/10.3390/cells11152380.

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