Imperial College London
Professor Dominic Withers

ProfessorDominicWithers

Faculty of Medicine, Institute of Clinical Sciences

Clinical Chair in Diabetes & Endocrinology
 
 
 
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Contact

 

d.withers

 
 
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Location

 

Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Herranz:2015:10.1038/ncb3225,
author = {Herranz, N and Gallage, S and Mellone, M and Wuestefeld, T and Klotz, S and Hanley, CJ and Raguz, S and Acosta, JC and Innes, AJ and Banito, A and Georgilis, A and Montoya, A and Wolter, K and Dharmalingam, G and Faull, P and Carroll, T and Martinez-Barbera, JP and Cutillas, P and Reisinger, F and Heikenwalder, M and Miller, RA and Withers, D and Zender, L and Thomas, GJ and Gill, J},
doi = {10.1038/ncb3225},
journal = {Nature Cell Biology},
pages = {1205--1217},
title = {mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype},
url = {http://dx.doi.org/10.1038/ncb3225},
volume = {17},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Herranz,N
AU  - Gallage,S
AU  - Mellone,M
AU  - Wuestefeld,T
AU  - Klotz,S
AU  - Hanley,CJ
AU  - Raguz,S
AU  - Acosta,JC
AU  - Innes,AJ
AU  - Banito,A
AU  - Georgilis,A
AU  - Montoya,A
AU  - Wolter,K
AU  - Dharmalingam,G
AU  - Faull,P
AU  - Carroll,T
AU  - Martinez-Barbera,JP
AU  - Cutillas,P
AU  - Reisinger,F
AU  - Heikenwalder,M
AU  - Miller,RA
AU  - Withers,D
AU  - Zender,L
AU  - Thomas,GJ
AU  - Gill,J
DO  - 10.1038/ncb3225
EP  - 1217
PY  - 2015///
SN  - 1476-4679
SP  - 1205
TI  - mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype
T2  - Nature Cell Biology
UR  - http://dx.doi.org/10.1038/ncb3225
UR  - https://www.nature.com/articles/ncb3225
UR  - http://hdl.handle.net/10044/1/32445
VL  - 17
ER  -
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