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rdf:type |
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lifeskim:mentions |
umls-concept:C0001721,
umls-concept:C0007589,
umls-concept:C0038952,
umls-concept:C0079419,
umls-concept:C0243125,
umls-concept:C0596290,
umls-concept:C0699900,
umls-concept:C1420010,
umls-concept:C1511938,
umls-concept:C1515877,
umls-concept:C1879547
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pubmed:issue |
12
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pubmed:dateCreated |
2010-1-21
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pubmed:abstractText |
Serum and glucocorticoid regulated kinase 1 (Sgk1) is a serine-threonine kinase that is activated by serum, steroids, insulin, vasopressin, and interleukin 2 at the transcriptional and post-translational levels. Sgk1 is also important in transduction of growth factors and steroid-dependent survival signals and may have a role in the development of resistance to cancer chemotherapy. In the present paper, we demonstrate that Sgk1 activates MDM2-dependent p53 ubiquitylation. The results were obtained in RKO cells and other cell lines by Sgk1-specific RNA silencing and were corroborated in an original mouse model as well as in transiently and in stably transfected HeLa cells expressing wild-type or dominant negative Sgk1 mutant. Sgk1 contributes to cell survival, cell-cycle progression, and epithelial de-differentiation. We also show that the effects of Sgk1 on the clonogenic potential of different cancer cells depend on the expression of wild-type p53. Since transcription of Sgk1 is activated by p53, we propose a finely tuned feedback model where Sgk1 down-regulates the expression of p53 by enhancing its mono- and polyubiquitylation.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1432-1440
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pubmed:author |
pubmed-author:AgostiValterV,
pubmed-author:AmatoRosarioR,
pubmed-author:BellacchioEmanueleE,
pubmed-author:CostaNicolaN,
pubmed-author:D'AntonaLuciaL,
pubmed-author:FuianoGiorgioG,
pubmed-author:LangFlorianF,
pubmed-author:MattarocciStefanoS,
pubmed-author:MennitiMirandaM,
pubmed-author:PaggiMarco GMG,
pubmed-author:PerrottiNicolaN,
pubmed-author:PorciattiGiovanniG,
pubmed-author:RinaldoCinziaC,
pubmed-author:SodduSilviaS
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pubmed:issnType |
Electronic
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pubmed:volume |
87
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1221-39
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:19756449-Animals,
pubmed-meshheading:19756449-Cell Death,
pubmed-meshheading:19756449-Cell Differentiation,
pubmed-meshheading:19756449-Cell Line,
pubmed-meshheading:19756449-Cell Proliferation,
pubmed-meshheading:19756449-Cell Survival,
pubmed-meshheading:19756449-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:19756449-HeLa Cells,
pubmed-meshheading:19756449-Humans,
pubmed-meshheading:19756449-Immediate-Early Proteins,
pubmed-meshheading:19756449-Male,
pubmed-meshheading:19756449-Mice,
pubmed-meshheading:19756449-Mice, Inbred BALB C,
pubmed-meshheading:19756449-Mice, Transgenic,
pubmed-meshheading:19756449-Protein-Serine-Threonine Kinases,
pubmed-meshheading:19756449-Proto-Oncogene Proteins c-mdm2,
pubmed-meshheading:19756449-Signal Transduction,
pubmed-meshheading:19756449-Transfection,
pubmed-meshheading:19756449-Tumor Suppressor Protein p53
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pubmed:year |
2009
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pubmed:articleTitle |
Sgk1 activates MDM2-dependent p53 degradation and affects cell proliferation, survival, and differentiation.
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pubmed:affiliation |
Department of Experimental and clinical Medicine G. Salvatore, Faculty of Medicine, University Magna Graecia at Catanzaro, Catanzaro, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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