New p53 target, phosphatase of regenerating liver 1 (PRL-1) downregulates p53

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dc.contributor.authorMin, S-Hko
dc.contributor.authorKim, D. M.ko
dc.contributor.authorHeo, Y-Sko
dc.contributor.authorKim, Y-Iko
dc.contributor.authorKim, Ho Minko
dc.contributor.authorKim, J.ko
dc.contributor.authorHan, Y-Mko
dc.contributor.authorKim, I-Cko
dc.contributor.authorYoo, Ook-Joonko
dc.date.accessioned2013-03-12T04:57:23Z-
dc.date.available2013-03-12T04:57:23Z-
dc.date.created2012-02-06-
dc.date.created2012-02-06-
dc.date.issued2009-01-
dc.identifier.citationONCOGENE, v.28, no.4, pp.545 - 554-
dc.identifier.issn0950-9232-
dc.identifier.urihttp://hdl.handle.net/10203/101376-
dc.description.abstractMost of the p53 target genes, all except MDM2, COP1 and PIRH2, perform functions in apoptosis, differentiation and cell cycle arrest. The aforementioned oncogenes downregulate p53 through a negative feedback mechanism, and thus contribute to tumor development. In this study, we report a new p53 target, PRL-1, which is believed to be a significant regulator in the development and metastasis of a variety of cancer types. Phosphatase of regenerating liver 1 (PRL-1) overexpression reduced the levels of endogenous and exogenous p53 proteins, and inhibited p53-mediated apoptosis. On the other hand, the ablation of PRL-1 by small interfering RNA (siRNA) increased p53 protein levels. The p53 downregulation was mediated by p53 ubiquitination and subsequent proteasomal degradation. Furthermore, p53 ubiquitination by PRL-1 was achieved through two independent pathways, by inducing PIRH2 transcription and by inducing MDM2 phosphorylation through Akt signaling. In addition, we showed that the PRL-1 gene harbors a p53 response element in the first intron, and its transcription is regulated by the p53 protein. These findings imply that the new oncogenic p53 target, PRL-1, may contribute to tumor development by the downregulation of p53 by a negative feedback mechanism.-
dc.languageEnglish-
dc.publisherNATURE PUBLISHING GROUP-
dc.subjectTUMOR-SUPPRESSOR PROTEIN-
dc.subjectGENE-EXPRESSION-
dc.subjectTYROSINE PHOSPHATASES-
dc.subjectCANCER-CELLS-
dc.subjectGROWTH-
dc.subjectACTIVATION-
dc.subjectMETASTASIS-
dc.subjectINVASION-
dc.subjectPHOSPHORYLATION-
dc.subjectMDM2-
dc.titleNew p53 target, phosphatase of regenerating liver 1 (PRL-1) downregulates p53-
dc.typeArticle-
dc.identifier.wosid000262866500008-
dc.identifier.scopusid2-s2.0-59149094764-
dc.type.rimsART-
dc.citation.volume28-
dc.citation.issue4-
dc.citation.beginningpage545-
dc.citation.endingpage554-
dc.citation.publicationnameONCOGENE-
dc.contributor.localauthorKim, Ho Min-
dc.contributor.localauthorYoo, Ook-Joon-
dc.contributor.nonIdAuthorMin, S-H-
dc.contributor.nonIdAuthorKim, D. M.-
dc.contributor.nonIdAuthorHeo, Y-S-
dc.contributor.nonIdAuthorKim, Y-I-
dc.contributor.nonIdAuthorKim, J.-
dc.contributor.nonIdAuthorHan, Y-M-
dc.contributor.nonIdAuthorKim, I-C-
dc.type.journalArticleArticle-
dc.subject.keywordAuthorp53 target-
dc.subject.keywordAuthorphosphatase of regenerating liver 1-
dc.subject.keywordAuthorPRL-1-
dc.subject.keywordAuthorEGR-
dc.subject.keywordAuthorPI3K-
dc.subject.keywordPlusTUMOR-SUPPRESSOR PROTEIN-
dc.subject.keywordPlusGENE-EXPRESSION-
dc.subject.keywordPlusTYROSINE PHOSPHATASES-
dc.subject.keywordPlusCANCER-CELLS-
dc.subject.keywordPlusGROWTH-
dc.subject.keywordPlusACTIVATION-
dc.subject.keywordPlusMETASTASIS-
dc.subject.keywordPlusINVASION-
dc.subject.keywordPlusPHOSPHORYLATION-
dc.subject.keywordPlusMDM2-
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