Suprainduction of p53 by disruption of 40S and 60S ribosome biogenesis leads to the activation of a novel G2/M checkpoint

Impairment of ribosome biogenesis leads to p53 induction and cell cycle arrest, a checkpoint involved in human disease. Induction of p53 is attributed to the binding and inhibition of human double minute 2 (Hdm2) by a subset of ribosomal proteins (RPs): RPS7, RPL5, RPL11, and RPL23. However, we foun...

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Detalles Bibliográficos
Autores: Fumagalli, Stefano, Ivanenkov, Vasily V., Teng, Teng, Thomas, George
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2012
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/172285
Acceso en línea:https://hdl.handle.net/2445/172285
Access Level:acceso abierto
Palabra clave:Cicle cel·lular
Fisiologia
Ribosomes
Metabolisme
Proteïnes supressores de tumors
Cell cycle
Physiology
Metabolism
Tumor suppressor protein
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spelling Suprainduction of p53 by disruption of 40S and 60S ribosome biogenesis leads to the activation of a novel G2/M checkpointFumagalli, StefanoIvanenkov, Vasily V.Teng, TengThomas, GeorgeCicle cel·lularFisiologiaRibosomesMetabolismeProteïnes supressores de tumorsCell cyclePhysiologyRibosomesMetabolismTumor suppressor proteinImpairment of ribosome biogenesis leads to p53 induction and cell cycle arrest, a checkpoint involved in human disease. Induction of p53 is attributed to the binding and inhibition of human double minute 2 (Hdm2) by a subset of ribosomal proteins (RPs): RPS7, RPL5, RPL11, and RPL23. However, we found that only RPL11 or RPL5, in a mutually dependent manner, elicit this response. We show that depletion of RPS7 or RPL23, like depletion of other RPs, except for RPL11 and RPL5, induces a p53 response and that the effects of RPS7 and RPL23 on p53 induction reported earlier may be ascribed to inhibition of global translation. Moreover, we made the surprising observation that codepletion of two essential RPs, one from each subunit, but not the same subunit, leads to suprainduction of p53. This led to the discovery that the previously proposed RPL11-dependent mechanism of p53 induction, thought to be caused by abrogation of 40S biogenesis and continued 60S biogenesis, is still operating, despite abrogation of 60S biogenesis. This response leads to both a G1 block and a novel G2/M block not observed when disrupting either subunit alone. Thus, induction of p53 is mediated by distinct mechanisms, with the data pointing to an essential role for ribosomal subunits beyond translation.Cold Spring Harbor Laboratory Press2020202020122020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion13 p.application/pdfhttps://hdl.handle.net/2445/172285Articles publicats en revistes (Ciències Fisiològiques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1101/gad.189951.112Genes & Development, 2012, vol. 26, num. 10, p. 1028-1040https://doi.org/10.1101/gad.189951.112(c) Fumagalli, Stefano et al., 2012info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1722852026-05-29T05:05:01Z
dc.title.none.fl_str_mv Suprainduction of p53 by disruption of 40S and 60S ribosome biogenesis leads to the activation of a novel G2/M checkpoint
title Suprainduction of p53 by disruption of 40S and 60S ribosome biogenesis leads to the activation of a novel G2/M checkpoint
spellingShingle Suprainduction of p53 by disruption of 40S and 60S ribosome biogenesis leads to the activation of a novel G2/M checkpoint
Fumagalli, Stefano
Cicle cel·lular
Fisiologia
Ribosomes
Metabolisme
Proteïnes supressores de tumors
Cell cycle
Physiology
Ribosomes
Metabolism
Tumor suppressor protein
title_short Suprainduction of p53 by disruption of 40S and 60S ribosome biogenesis leads to the activation of a novel G2/M checkpoint
title_full Suprainduction of p53 by disruption of 40S and 60S ribosome biogenesis leads to the activation of a novel G2/M checkpoint
title_fullStr Suprainduction of p53 by disruption of 40S and 60S ribosome biogenesis leads to the activation of a novel G2/M checkpoint
title_full_unstemmed Suprainduction of p53 by disruption of 40S and 60S ribosome biogenesis leads to the activation of a novel G2/M checkpoint
title_sort Suprainduction of p53 by disruption of 40S and 60S ribosome biogenesis leads to the activation of a novel G2/M checkpoint
dc.creator.none.fl_str_mv Fumagalli, Stefano
Ivanenkov, Vasily V.
Teng, Teng
Thomas, George
author Fumagalli, Stefano
author_facet Fumagalli, Stefano
Ivanenkov, Vasily V.
Teng, Teng
Thomas, George
author_role author
author2 Ivanenkov, Vasily V.
Teng, Teng
Thomas, George
author2_role author
author
author
dc.subject.none.fl_str_mv Cicle cel·lular
Fisiologia
Ribosomes
Metabolisme
Proteïnes supressores de tumors
Cell cycle
Physiology
Ribosomes
Metabolism
Tumor suppressor protein
topic Cicle cel·lular
Fisiologia
Ribosomes
Metabolisme
Proteïnes supressores de tumors
Cell cycle
Physiology
Ribosomes
Metabolism
Tumor suppressor protein
description Impairment of ribosome biogenesis leads to p53 induction and cell cycle arrest, a checkpoint involved in human disease. Induction of p53 is attributed to the binding and inhibition of human double minute 2 (Hdm2) by a subset of ribosomal proteins (RPs): RPS7, RPL5, RPL11, and RPL23. However, we found that only RPL11 or RPL5, in a mutually dependent manner, elicit this response. We show that depletion of RPS7 or RPL23, like depletion of other RPs, except for RPL11 and RPL5, induces a p53 response and that the effects of RPS7 and RPL23 on p53 induction reported earlier may be ascribed to inhibition of global translation. Moreover, we made the surprising observation that codepletion of two essential RPs, one from each subunit, but not the same subunit, leads to suprainduction of p53. This led to the discovery that the previously proposed RPL11-dependent mechanism of p53 induction, thought to be caused by abrogation of 40S biogenesis and continued 60S biogenesis, is still operating, despite abrogation of 60S biogenesis. This response leads to both a G1 block and a novel G2/M block not observed when disrupting either subunit alone. Thus, induction of p53 is mediated by distinct mechanisms, with the data pointing to an essential role for ribosomal subunits beyond translation.
publishDate 2012
dc.date.none.fl_str_mv 2012
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/172285
url https://hdl.handle.net/2445/172285
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1101/gad.189951.112
Genes & Development, 2012, vol. 26, num. 10, p. 1028-1040
https://doi.org/10.1101/gad.189951.112
dc.rights.none.fl_str_mv (c) Fumagalli, Stefano et al., 2012
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Fumagalli, Stefano et al., 2012
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 13 p.
application/pdf
dc.publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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