Genetic interrogation of replicative senescence uncovers a dual role for USP28 in coordinating the p53 and GATA4 branches of the senescence program

Senescence is a terminal differentiation program that halts the growth of damaged cells and must be circumvented for cancer to arise. Here we describe a panel of genetic screens to identify genes required for replicative senescence. We uncover a role in senescence for the potent tumor suppressor and...

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Autores principales: Mazzucco, Anna E., Smogorzewska, Agata, Kang, Chanhee, Luo, Ji, Schlabach, Michael R., Xu, Qikai, Patel, Rupesh, Elledge, Stephen J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Research Communication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710139/
https://www.ncbi.nlm.nih.gov/pubmed/29089421
http://dx.doi.org/10.1101/gad.304857.117
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author Mazzucco, Anna E.
Smogorzewska, Agata
Kang, Chanhee
Luo, Ji
Schlabach, Michael R.
Xu, Qikai
Patel, Rupesh
Elledge, Stephen J.
author_facet Mazzucco, Anna E.
Smogorzewska, Agata
Kang, Chanhee
Luo, Ji
Schlabach, Michael R.
Xu, Qikai
Patel, Rupesh
Elledge, Stephen J.
author_sort Mazzucco, Anna E.
collection PubMed
description Senescence is a terminal differentiation program that halts the growth of damaged cells and must be circumvented for cancer to arise. Here we describe a panel of genetic screens to identify genes required for replicative senescence. We uncover a role in senescence for the potent tumor suppressor and ATM substrate USP28. USP28 controls activation of both the TP53 branch and the GATA4/NFkB branch that controls the senescence-associated secretory phenotype (SASP). These results suggest a role for ubiquitination in senescence and imply a common node downstream from ATM that links the TP53 and GATA4 branches of the senescence response.
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spelling pubmed-57101392018-04-01 Genetic interrogation of replicative senescence uncovers a dual role for USP28 in coordinating the p53 and GATA4 branches of the senescence program Mazzucco, Anna E. Smogorzewska, Agata Kang, Chanhee Luo, Ji Schlabach, Michael R. Xu, Qikai Patel, Rupesh Elledge, Stephen J. Genes Dev Research Communication Senescence is a terminal differentiation program that halts the growth of damaged cells and must be circumvented for cancer to arise. Here we describe a panel of genetic screens to identify genes required for replicative senescence. We uncover a role in senescence for the potent tumor suppressor and ATM substrate USP28. USP28 controls activation of both the TP53 branch and the GATA4/NFkB branch that controls the senescence-associated secretory phenotype (SASP). These results suggest a role for ubiquitination in senescence and imply a common node downstream from ATM that links the TP53 and GATA4 branches of the senescence response. Cold Spring Harbor Laboratory Press 2017-10-01 /pmc/articles/PMC5710139/ /pubmed/29089421 http://dx.doi.org/10.1101/gad.304857.117 Text en © 2017 Mazzucco et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Communication
Mazzucco, Anna E.
Smogorzewska, Agata
Kang, Chanhee
Luo, Ji
Schlabach, Michael R.
Xu, Qikai
Patel, Rupesh
Elledge, Stephen J.
Genetic interrogation of replicative senescence uncovers a dual role for USP28 in coordinating the p53 and GATA4 branches of the senescence program
title Genetic interrogation of replicative senescence uncovers a dual role for USP28 in coordinating the p53 and GATA4 branches of the senescence program
title_full Genetic interrogation of replicative senescence uncovers a dual role for USP28 in coordinating the p53 and GATA4 branches of the senescence program
title_fullStr Genetic interrogation of replicative senescence uncovers a dual role for USP28 in coordinating the p53 and GATA4 branches of the senescence program
title_full_unstemmed Genetic interrogation of replicative senescence uncovers a dual role for USP28 in coordinating the p53 and GATA4 branches of the senescence program
title_short Genetic interrogation of replicative senescence uncovers a dual role for USP28 in coordinating the p53 and GATA4 branches of the senescence program
title_sort genetic interrogation of replicative senescence uncovers a dual role for usp28 in coordinating the p53 and gata4 branches of the senescence program
topic Research Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710139/
https://www.ncbi.nlm.nih.gov/pubmed/29089421
http://dx.doi.org/10.1101/gad.304857.117
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