Počet záznamů: 1
Endogenous PP2A inhibitor CIP2A degradation by chaperone-mediated autophagy contributes to the antitumor effect of mitochondrial complex I inhibition
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SYSNO ASEP 0575022 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Endogenous PP2A inhibitor CIP2A degradation by chaperone-mediated autophagy contributes to the antitumor effect of mitochondrial complex I inhibition Tvůrce(i) Cazzoli, G. (IT)
Romeo, F. (IT)
Pallavicini, A. (IT)
Peri, S. (IT)
Romanenghi, M. (IT)
Perez-Valencia, J. A. (DE)
Hagag, E. (DE)
Ferrucci, F. (DE)
Elgendy, Mohamed (UMG-J)
Vittorioso, P. (IT)
Pece, S. (IT)
Foiani, M. (IT)
Westermarck, J. (FI)
Minucci, S. (IT)Celkový počet autorů 14 Číslo článku 112616 Zdroj.dok. Cell Reports. - : Cell Press - ISSN 2211-1247
Roč. 42, č. 6 (2023)Poč.str. 16 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova oxidative phosphorylation ; tumor cell ; cancer therapy ; regulator of CIP2A ; PP2A inhibitor Obor OECD Oncology CEP LX22NPO5102 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy GJ19-22156Y GA ČR - Grantová agentura ČR Způsob publikování Open access Institucionální podpora UMG-J - RVO:68378050 UT WOS 001019081700001 EID SCOPUS 85161282536 DOI 10.1016/j.celrep.2023.112616 Anotace Combined inhibition of oxidative phosphorylation (OXPHOS) and glycolysis has been shown to activate a PP2A-dependent signaling pathway, leading to tumor cell death. Here, we analyze highly selective mitochon-drial complex I or III inhibitors in vitro and in vivo to elucidate the molecular mechanisms leading to cell death following OXPHOS inhibition. We show that IACS-010759 treatment (complex I inhibitor) induces a reactive oxygen species (ROS)-dependent dissociation of CIP2A from PP2A, leading to its destabilization and degra-dation through chaperone-mediated autophagy. Mitochondrial complex III inhibition has analogous effects. We establish that activation of the PP2A holoenzyme containing B568 regulatory subunit selectively mediates tumor cell death, while the arrest in proliferation that is observed upon IACS-010759 treatment does not depend on the PP2A-B568 complex. These studies provide a molecular characterization of the events sub-sequent to the alteration of critical bioenergetic pathways and help to refine clinical studies aimed to exploit metabolic vulnerabilities of tumor cells. Pracoviště Ústav molekulární genetiky Kontakt Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Rok sběru 2024 Elektronická adresa https://www.sciencedirect.com/science/article/pii/S2211124723006277?via%3Dihub
Počet záznamů: 1