Translation inhibition and suppression of stress granules formation by cisplatin

Platinum-based antineoplastic drugs, such as cisplatin, are commonly used to induce tumor cell death. Cisplatin is believed to induce apoptosis as a result of cisplatin-DNA adducts that inhibit DNA and RNA synthesis. Although idea that DNA damage underlines anti-proliferative effects of cisplatin is...

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Autores principales:	Paulina Pietras, Anaïs Aulas, Marta M. Fay, Marta Leśniczak-Staszak, Mateusz Sowiński, Shawn M. Lyons, Witold Szaflarski, Pavel Ivanov
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Chemotherapy Cisplatin Stress granules Translation initiation Stress response Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/e1950fe9973046578127c4bb440eb387
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spelling	oai:doaj.org-article:e1950fe9973046578127c4bb440eb3872021-12-02T04:59:05ZTranslation inhibition and suppression of stress granules formation by cisplatin0753-332210.1016/j.biopha.2021.112382https://doaj.org/article/e1950fe9973046578127c4bb440eb3872022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0753332221011665https://doaj.org/toc/0753-3322Platinum-based antineoplastic drugs, such as cisplatin, are commonly used to induce tumor cell death. Cisplatin is believed to induce apoptosis as a result of cisplatin-DNA adducts that inhibit DNA and RNA synthesis. Although idea that DNA damage underlines anti-proliferative effects of cisplatin is dominant in cancer research, there is a poor correlation between the degree of the cell sensitivity to cisplatin and the extent of DNA platination. Here, we examined possible effects of cisplatin on post-transcriptional gene regulation that may contribute to cisplatin-mediated cytotoxicity. We show that cisplatin suppresses formation of stress granules (SGs), pro-survival RNA granules with multiple roles in cellular metabolism. Mechanistically, cisplatin inhibits cellular translation to promote disassembly of polysomes and aggregation of ribosomal subunits. As SGs are in equilibrium with polysomes, cisplatin-induced shift towards ribosomal aggregation suppresses SG formation. Our data uncover previously unknown effects of cisplatin on RNA metabolism.Paulina PietrasAnaïs AulasMarta M. FayMarta Leśniczak-StaszakMateusz SowińskiShawn M. LyonsWitold SzaflarskiPavel IvanovElsevierarticleChemotherapyCisplatinStress granulesTranslation initiationStress responseTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 145, Iss , Pp 112382- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Chemotherapy Cisplatin Stress granules Translation initiation Stress response Therapeutics. Pharmacology RM1-950
spellingShingle	Chemotherapy Cisplatin Stress granules Translation initiation Stress response Therapeutics. Pharmacology RM1-950 Paulina Pietras Anaïs Aulas Marta M. Fay Marta Leśniczak-Staszak Mateusz Sowiński Shawn M. Lyons Witold Szaflarski Pavel Ivanov Translation inhibition and suppression of stress granules formation by cisplatin
description	Platinum-based antineoplastic drugs, such as cisplatin, are commonly used to induce tumor cell death. Cisplatin is believed to induce apoptosis as a result of cisplatin-DNA adducts that inhibit DNA and RNA synthesis. Although idea that DNA damage underlines anti-proliferative effects of cisplatin is dominant in cancer research, there is a poor correlation between the degree of the cell sensitivity to cisplatin and the extent of DNA platination. Here, we examined possible effects of cisplatin on post-transcriptional gene regulation that may contribute to cisplatin-mediated cytotoxicity. We show that cisplatin suppresses formation of stress granules (SGs), pro-survival RNA granules with multiple roles in cellular metabolism. Mechanistically, cisplatin inhibits cellular translation to promote disassembly of polysomes and aggregation of ribosomal subunits. As SGs are in equilibrium with polysomes, cisplatin-induced shift towards ribosomal aggregation suppresses SG formation. Our data uncover previously unknown effects of cisplatin on RNA metabolism.
format	article
author	Paulina Pietras Anaïs Aulas Marta M. Fay Marta Leśniczak-Staszak Mateusz Sowiński Shawn M. Lyons Witold Szaflarski Pavel Ivanov
author_facet	Paulina Pietras Anaïs Aulas Marta M. Fay Marta Leśniczak-Staszak Mateusz Sowiński Shawn M. Lyons Witold Szaflarski Pavel Ivanov
author_sort	Paulina Pietras
title	Translation inhibition and suppression of stress granules formation by cisplatin
title_short	Translation inhibition and suppression of stress granules formation by cisplatin
title_full	Translation inhibition and suppression of stress granules formation by cisplatin
title_fullStr	Translation inhibition and suppression of stress granules formation by cisplatin
title_full_unstemmed	Translation inhibition and suppression of stress granules formation by cisplatin
title_sort	translation inhibition and suppression of stress granules formation by cisplatin
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/e1950fe9973046578127c4bb440eb387
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Translation inhibition and suppression of stress granules formation by cisplatin

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