PuSH - Publication Server of Helmholtz Zentrum München: mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype.

Information

Clues to quality of journals

Open Access Policy of Helmholtz Association 2016

CC Licencences

Publication Metrics

Navigation

Home

Deutsch

EVA: Electronic Publishing

New EVA Application

Research

Advanced Search

Browse by ...

... HMGU-Authors/Consortia

... Organizational Structure

... Journal

... Publication Type

... Research Data

... Arbeitsgruppen

... Publication Year

Publication overview

Statistics

Statistics (last 5 years)

OA Publications

Publish

Submit Publication

Import publication from...

...EVA

Report missing publication

Highlights

Support & Contact

Contact persons

Help

Data protection

Helmholtz Open Science

JANE Journal Estimator

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Herranz, N.* ; Gallage, S.* ; Mellone, M.* ; Wuestefeld, T.* ; Klotz, S.* ; Hanley, C.J.* ; Raguz, S.* ; Acosta, J.C.* ; Innes, A.J.* ; Banito, A.* ; Georgilis, A.* ; Montoya, A.* ; Wolter, K.* ; Dharmalingam, G.* ; Faull, P.* ; Carroll, T.* ; Martínez-Barbera, J.P.* ; Cutillas, P.* ; Reisinger, F. ; Heikenwälder, M. ; Miller, R.A.* ; Withers, D.* ; Zender, L.* ; Thomas, G.J.* ; Gil, J.*

mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype.

Nat. Cell Biol. 17, 1205-1217 (2015)

Supplement

DOI

PMC

Open Access Green as soon as Postprint is submitted to ZB.

Abstract
Metrics
Extra information

Senescent cells secrete a combination of factors collectively known as the senescence-associated secretory phenotype (SASP). The SASP reinforces senescence and activates an immune surveillance response, but it can also show pro-tumorigenic properties and contribute to age-related pathologies. In a drug screen to find new SASP regulators, we uncovered the mTOR inhibitor rapamycin as a potent SASP suppressor. Here we report a mechanism by which mTOR controls the SASP by differentially regulating the translation of the MK2 (also known as MAPKAPK2) kinase through 4EBP1. In turn, MAPKAPK2 phosphorylates the RNA-binding protein ZFP36L1 during senescence, inhibiting its ability to degrade the transcripts of numerous SASP components. Consequently, mTOR inhibition or constitutive activation of ZFP36L1 impairs the non-cell-autonomous effects of senescent cells in both tumour-suppressive and tumour-promoting contexts. Altogether, our results place regulation of the SASP as a key mechanism by which mTOR could influence cancer, age-related diseases and immune responses.

Impact Factor

Scopus SNIP

Web of Science
Times Cited

Scopus
Cited By

Altmetric

19.679

3.457

304

402