SOCS1, a novel interaction partner of p53 controlling oncogene-induced senescence.

Aging
Frédérick A MalletteG Ferbeyre

Abstract

Members of the signal transducers and activators of transcription (STATs) family of proteins, which connect cytokine signaling to activation of transcription, are frequently activated in human cancers. Suppressors of cytokine signaling (SOCS) are transcriptional targets of activated STAT proteins that negatively control STAT signaling. SOCS1 expression is silenced in multiple human cancers suggesting a tumor suppressor role for this protein. However, SOCS1 not only regulates STAT signaling but can also localize to the nucleus and directly interact with the p53 tumor suppressor through its central SH2 domain. Furthermore, SOCS1 contributes to p53 activation and phosphorylation on serine 15 by forming a ternary complex with ATM or ATR. Through this mechanism SOCS1 regulates the process of oncogene-induced senescence, which is a very important tumor suppressor response. A mutant SOCS1 lacking the SOCS box cannot interact with ATM/ATR, stimulate p53 or induce the senescence phenotype, suggesting that the SOCS box recruits DNA damage activated kinases to its interaction partners bound to its SH2 domain. Proteomic analysis of SOCS1 interaction partners revealed other potential targets of SOCS1 in the DNA damage response. These newly ...Continue Reading

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Citations

Oct 26, 2012·Cell Cycle·Anna Bianchi-Smiraglia, Mikhail A Nikiforov
Jan 15, 2014·JAK-STAT·Hirotada KojimaKoichi Nakajima
Dec 6, 2016·Frontiers in Immunology·Jana ZimmerAlexander Dalpke
Oct 31, 2017·Aging·Emmanuelle Saint-GermainGerardo Ferbeyre
Nov 20, 2018·Frontiers in Oncology·Weifen ZhangWentong Li
Sep 29, 2019·Cancers·Sebastian IgelmannGerardo Ferbeyre
Nov 20, 2012·Cell Cycle·Francesca GrespiGerry Melino
Nov 21, 2012·Cell Cycle·Ivano AmelioGerry Melino
Sep 24, 2015·Scientific Reports·William S TobelaimCaroline Saucier
Apr 17, 2019·Cancers·Yeon-Hee YoonJe-Yoel Cho
May 21, 2019·Frontiers in Pharmacology·Jatin Sharma, Joseph Larkin
Apr 30, 2019·Frontiers in Immunology·Christine I Alston, Richard D Dix
Sep 21, 2011·Cell Biology International·Tai LiHongjuan Cui
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Oct 26, 2011·International Journal of Cancer. Journal International Du Cancer·Jing ZhangXiu-Bao Ren
Apr 24, 2014·Molecular Biology International·Walid SasiKefah Mokbel
Feb 7, 2015·Aging and Disease·Amanda Piano, Vladimir I Titorenko
May 19, 2019·Cancer Research·Emmanuelle Saint-GermainGerardo Ferbeyre
Mar 6, 2021·Frontiers in Pharmacology·Yuting ZhuangMingyu Zhang

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Methods Mentioned

BETA
ubiquitination
sumoylation
pulldown

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