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}
}
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 -
