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.

Základní údaje

Originální název

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

Autoři

ZRIMSEK, Masa, Hana KUCHAŘÍKOVÁ (203 Česká republika, domácí), Kristina DRAGANIC, Pavlína PÍREK (203 Česká republika, domácí), Verena Heiss SPORNBERGER, Lisa WINKELMAYER, Melanie R HASSLER, Gabriela LOCHMANOVÁ (203 Česká republika, domácí), Zbyněk ZDRÁHAL (203 Česká republika, garant, domácí) a Gerda EGGER

Vydání

CELLS, MDPI, 2022, 2073-4409

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10601 Cell biology

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Impakt faktor

Impact factor: 6.000

Kód RIV

RIV/00216224:14740/22:00128595

Organizační jednotka

Středoevropský technologický institut

DOI

UT WoS

000839344600001

Klíčová slova anglicky

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

Štítky

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 10. 10. 2024 15:04, Ing. Martina Blahová

Anotace

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.

Návaznosti

EF18_046/0015974, projekt VaV
Název: Modernizace České infrastruktury pro integrativní strukturní biologii
GF19-29701L, projekt VaV
Název: Funkce HDAC1 v T-buněčných lymfomech
Investor: Grantová agentura ČR, Funkce HDAC1 v T-buněčných lymfomech, Partnerská agentura (Rakousko)
LM2018127, projekt VaV
Název: Česká infrastruktura pro integrativní strukturní biologii (Akronym: CIISB)
Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Czech Infrastructure for Integrative Structural Biology
LM2018140, projekt VaV
Název: e-Infrastruktura CZ (Akronym: e-INFRA CZ)
Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, e-Infrastruktura CZ
90127, velká výzkumná infrastruktura
Název: CIISB II