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Cooperative actions of p21 WAF 1 and p53 induce Slug protein degradation and suppress cell invasion
Author(s) -
Kim Jongdoo,
Bae Seunghee,
An Sungkwan,
Park Jong Kuk,
Kim Eun Mi,
Hwang SangGu,
Kim WunJae,
Um HongDuck
Publication year - 2014
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201438587
Subject(s) - slug , microbiology and biotechnology , transcription factor , suppressor , mdm2 , mutant , cell , function (biology) , biology , transcription (linguistics) , chemistry , cell culture , cancer research , gene , biochemistry , genetics , linguistics , philosophy
How the p53 transcription factor/tumor suppressor inhibits cell invasion is poorly understood. We demonstrate that this function of p53 requires its direct interaction with p21 WAF 1 , a transcriptional target of p53, and that both p21 and p53 bind to Slug, which promotes cell invasion. Functional studies reveal that p21 and p53 cooperate to facilitate Mdm2‐dependent Slug degradation and that this p53 function is mimicked by p53 R273H , a mutant lacking trans‐activating activity. These actions of p21 and p53 are induced by γ‐irradiation of cells and also operate in vivo . This is the first study to elucidate a mechanism involving p53 and p21 cooperation.