Senescence-associated ribosome biogenesis defects contributes to cell cycle arrest through the Rb pathway

Frédéric Lessard, Sebastian Igelmann, Christian Trahan, Geneviève Huot, Emmanuelle Saint-Germain, Lian Mignacca, Neylen Del Toro, Stéphane Lopes-Paciencia, Benjamin Le Calve, Marinieve Montero, Xavier Deschënes-Simard, Marina Bury, Olga Moiseeva, Marie-Camille Rowell, Marlene Oeffinger, Cornelia E. Zorca, Daniel Zenklusen, Léa Brakier-Gingras, Véronique Bourdeau, Gerardo Ferbeyre

Résultats de recherche: Contribution à un journal/une revueArticle

Résumé

Cellular senescence is a tumour suppressor programme characterized by a stable cell cycle arrest. Here we report that cellular senescence triggered by a variety of stimuli leads to diminished ribosome biogenesis and the accumulation of both rRNA precursors and ribosomal proteins. These defects were associated with reduced expression of several ribosome biogenesis factors, the knockdown of which was also sufficient to induce senescence. Genetic analysis revealed that Rb but not p53 was required for the senescence response to altered ribosome biogenesis. Mechanistically, the ribosomal protein S14 (RPS14 or uS11) accumulates in the soluble non-ribosomal fraction of senescent cells, where it binds and inhibits CDK4 (cyclin-dependent kinase 4). Overexpression of RPS14 is sufficient to inhibit Rb phosphorylation, inducing cell cycle arrest and senescence. Here we describe a mechanism for maintaining the senescent cell cycle arrest that may be relevant for cancer therapy, as well as biomarkers to identify senescent cells.

langue originaleAnglais
Pages (de - à)789-799
Nombre de pages11
journalnature cell biology
Volume20
Numéro de publication7
Les DOIs
étatPublié - 1 juil. 2018

Empreinte digitale

Cell Aging
Cell Cycle Checkpoints
Ribosomes
Cyclin-Dependent Kinase 4
Ribosomal Proteins
RNA Precursors
Neoplasms
Biomarkers
Phosphorylation
Therapeutics

Citer ceci

Lessard, F., Igelmann, S., Trahan, C., Huot, G., Saint-Germain, E., Mignacca, L., ... Ferbeyre, G. (2018). Senescence-associated ribosome biogenesis defects contributes to cell cycle arrest through the Rb pathway. nature cell biology, 20(7), 789-799. https://doi.org/10.1038/s41556-018-0127-y
Lessard, Frédéric ; Igelmann, Sebastian ; Trahan, Christian ; Huot, Geneviève ; Saint-Germain, Emmanuelle ; Mignacca, Lian ; Del Toro, Neylen ; Lopes-Paciencia, Stéphane ; Le Calve, Benjamin ; Montero, Marinieve ; Deschënes-Simard, Xavier ; Bury, Marina ; Moiseeva, Olga ; Rowell, Marie-Camille ; Oeffinger, Marlene ; Zorca, Cornelia E. ; Zenklusen, Daniel ; Brakier-Gingras, Léa ; Bourdeau, Véronique ; Ferbeyre, Gerardo. / Senescence-associated ribosome biogenesis defects contributes to cell cycle arrest through the Rb pathway. Dans: nature cell biology. 2018 ; Vol 20, Numéro 7. p. 789-799.
@article{b44ff10ebcc6419d9f9bcfc49f10a83a,
title = "Senescence-associated ribosome biogenesis defects contributes to cell cycle arrest through the Rb pathway",
abstract = "Cellular senescence is a tumour suppressor programme characterized by a stable cell cycle arrest. Here we report that cellular senescence triggered by a variety of stimuli leads to diminished ribosome biogenesis and the accumulation of both rRNA precursors and ribosomal proteins. These defects were associated with reduced expression of several ribosome biogenesis factors, the knockdown of which was also sufficient to induce senescence. Genetic analysis revealed that Rb but not p53 was required for the senescence response to altered ribosome biogenesis. Mechanistically, the ribosomal protein S14 (RPS14 or uS11) accumulates in the soluble non-ribosomal fraction of senescent cells, where it binds and inhibits CDK4 (cyclin-dependent kinase 4). Overexpression of RPS14 is sufficient to inhibit Rb phosphorylation, inducing cell cycle arrest and senescence. Here we describe a mechanism for maintaining the senescent cell cycle arrest that may be relevant for cancer therapy, as well as biomarkers to identify senescent cells.",
author = "Fr{\'e}d{\'e}ric Lessard and Sebastian Igelmann and Christian Trahan and Genevi{\`e}ve Huot and Emmanuelle Saint-Germain and Lian Mignacca and {Del Toro}, Neylen and St{\'e}phane Lopes-Paciencia and {Le Calve}, Benjamin and Marinieve Montero and Xavier Desch{\"e}nes-Simard and Marina Bury and Olga Moiseeva and Marie-Camille Rowell and Marlene Oeffinger and Zorca, {Cornelia E.} and Daniel Zenklusen and L{\'e}a Brakier-Gingras and V{\'e}ronique Bourdeau and Gerardo Ferbeyre",
year = "2018",
month = "7",
day = "1",
doi = "10.1038/s41556-018-0127-y",
language = "English",
volume = "20",
pages = "789--799",
journal = "nature cell biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "7",

}

Lessard, F, Igelmann, S, Trahan, C, Huot, G, Saint-Germain, E, Mignacca, L, Del Toro, N, Lopes-Paciencia, S, Le Calve, B, Montero, M, Deschënes-Simard, X, Bury, M, Moiseeva, O, Rowell, M-C, Oeffinger, M, Zorca, CE, Zenklusen, D, Brakier-Gingras, L, Bourdeau, V & Ferbeyre, G 2018, 'Senescence-associated ribosome biogenesis defects contributes to cell cycle arrest through the Rb pathway', nature cell biology, VOL. 20, Numéro 7, p. 789-799. https://doi.org/10.1038/s41556-018-0127-y

Senescence-associated ribosome biogenesis defects contributes to cell cycle arrest through the Rb pathway. / Lessard, Frédéric; Igelmann, Sebastian; Trahan, Christian; Huot, Geneviève; Saint-Germain, Emmanuelle; Mignacca, Lian; Del Toro, Neylen; Lopes-Paciencia, Stéphane; Le Calve, Benjamin; Montero, Marinieve; Deschënes-Simard, Xavier; Bury, Marina; Moiseeva, Olga; Rowell, Marie-Camille; Oeffinger, Marlene; Zorca, Cornelia E.; Zenklusen, Daniel; Brakier-Gingras, Léa; Bourdeau, Véronique; Ferbeyre, Gerardo.

Dans: nature cell biology, Vol 20, Numéro 7, 01.07.2018, p. 789-799.

Résultats de recherche: Contribution à un journal/une revueArticle

TY - JOUR

T1 - Senescence-associated ribosome biogenesis defects contributes to cell cycle arrest through the Rb pathway

AU - Lessard, Frédéric

AU - Igelmann, Sebastian

AU - Trahan, Christian

AU - Huot, Geneviève

AU - Saint-Germain, Emmanuelle

AU - Mignacca, Lian

AU - Del Toro, Neylen

AU - Lopes-Paciencia, Stéphane

AU - Le Calve, Benjamin

AU - Montero, Marinieve

AU - Deschënes-Simard, Xavier

AU - Bury, Marina

AU - Moiseeva, Olga

AU - Rowell, Marie-Camille

AU - Oeffinger, Marlene

AU - Zorca, Cornelia E.

AU - Zenklusen, Daniel

AU - Brakier-Gingras, Léa

AU - Bourdeau, Véronique

AU - Ferbeyre, Gerardo

PY - 2018/7/1

Y1 - 2018/7/1

N2 - Cellular senescence is a tumour suppressor programme characterized by a stable cell cycle arrest. Here we report that cellular senescence triggered by a variety of stimuli leads to diminished ribosome biogenesis and the accumulation of both rRNA precursors and ribosomal proteins. These defects were associated with reduced expression of several ribosome biogenesis factors, the knockdown of which was also sufficient to induce senescence. Genetic analysis revealed that Rb but not p53 was required for the senescence response to altered ribosome biogenesis. Mechanistically, the ribosomal protein S14 (RPS14 or uS11) accumulates in the soluble non-ribosomal fraction of senescent cells, where it binds and inhibits CDK4 (cyclin-dependent kinase 4). Overexpression of RPS14 is sufficient to inhibit Rb phosphorylation, inducing cell cycle arrest and senescence. Here we describe a mechanism for maintaining the senescent cell cycle arrest that may be relevant for cancer therapy, as well as biomarkers to identify senescent cells.

AB - Cellular senescence is a tumour suppressor programme characterized by a stable cell cycle arrest. Here we report that cellular senescence triggered by a variety of stimuli leads to diminished ribosome biogenesis and the accumulation of both rRNA precursors and ribosomal proteins. These defects were associated with reduced expression of several ribosome biogenesis factors, the knockdown of which was also sufficient to induce senescence. Genetic analysis revealed that Rb but not p53 was required for the senescence response to altered ribosome biogenesis. Mechanistically, the ribosomal protein S14 (RPS14 or uS11) accumulates in the soluble non-ribosomal fraction of senescent cells, where it binds and inhibits CDK4 (cyclin-dependent kinase 4). Overexpression of RPS14 is sufficient to inhibit Rb phosphorylation, inducing cell cycle arrest and senescence. Here we describe a mechanism for maintaining the senescent cell cycle arrest that may be relevant for cancer therapy, as well as biomarkers to identify senescent cells.

UR - http://www.scopus.com/inward/record.url?scp=85048977092&partnerID=8YFLogxK

U2 - 10.1038/s41556-018-0127-y

DO - 10.1038/s41556-018-0127-y

M3 - Article

VL - 20

SP - 789

EP - 799

JO - nature cell biology

JF - nature cell biology

SN - 1465-7392

IS - 7

ER -