title: Cooperative actions of p21WAF1 and p53 induce Slug protein degradation and suppress cell invasion.
abstract: 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(WAF1), 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.
authors.affiliation: Division of Radiation Cancer Biology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea Department of Radiological Cancer Medicine, University of Science and Technology, Seoul, Korea.
authors.forename: Jongdoo
authors.initials: J
authors.lastname: Kim
authors.affiliation: Molecular-Targeted Drug Research Center, Konkuk University, Seoul, Korea.
authors.forename: Seunghee
authors.initials: S
authors.lastname: Bae
authors.affiliation: Molecular-Targeted Drug Research Center, Konkuk University, Seoul, Korea.
authors.forename: Sungkwan
authors.initials: S
authors.lastname: An
authors.affiliation: Division of Radiation Cancer Biology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea.
authors.forename: Jong Kuk
authors.initials: JK
authors.lastname: Park
authors.affiliation: Division of Radiation Cancer Biology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea.
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Kim
authors.affiliation: Division of Radiation Cancer Biology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea.
authors.forename: Sang-Gu
authors.initials: SG
authors.lastname: Hwang
authors.affiliation: Department of Urology, Chungbuk National University, Chungju, Korea.
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: Division of Radiation Cancer Biology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea Department of Radiological Cancer Medicine, University of Science and Technology, Seoul, Korea hdum@kcch.re.kr.
authors.forename: Hong-Duck
authors.initials: HD
authors.lastname: Um
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D005720:Gamma Rays; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000235:genetics*; D011485:Protein Binding / Q000528:radiation effects; D059748:Proteolysis / Q000528:radiation effects; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
keywords: Cancer; Slug; invasion; p21; p53