Document Detail


p27kip1 protein levels reflect a nexus of oncogenic signaling during cell transformation.
MedLine Citation:
PMID:  22511779     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
SV40 small t-antigen (ST) collaborates with SV40 large T-antigen (LT) and activated rasv12 to promote transformation in a variety of immortalized human cells. A number of oncogenes or the disruption of the general serine-threonine phosphatase protein phosphatase 2A (PP2A) can replace ST in this paradigm. However, the relationship between these oncogenes and PP2A activity is not clear. To address this, we queried the connectivity of these molecules in silico. We found that p27 was connected to each of those oncogenes that could substitute for ST. We further determined that p27 loss can substitute for the expression of ST during transformation of both rodent and human cells. Conversely, knock-in cells expressing the degradation-resistant S10A and T187A mutants of p27 were resistant to the transforming activities of ST. This suggests that p27 is an important target of the tumor-suppressive effects of PP2A and likely an important target of the multitude of cellular oncoproteins that emulate the transforming function of ST.
Authors:
Jeffrey P Miller; Nancy Yeh; Christoph P Hofstetter; Doruk Keskin; Andrew S Goldstein; Andrew Koff
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-04-17
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-11     Completed Date:  2012-09-21     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  19775-85     Citation Subset:  IM    
Affiliation:
Department of Molecular Biology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Substitution
Animals
Antigens, Polyomavirus Transforming / genetics,  metabolism*
Cell Line
Cell Transformation, Neoplastic / genetics,  metabolism*,  pathology
Cyclin-Dependent Kinase Inhibitor p27 / genetics,  metabolism*
Humans
Mice
Mutation, Missense
Protein Phosphatase 2 / genetics,  metabolism*
Proteolysis
Grant Support
ID/Acronym/Agency:
CA89563/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, Polyomavirus Transforming; 0/CDKN1B protein, human; 0/Cdkn1b protein, mouse; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; EC 3.1.3.16/Protein Phosphatase 2
Comments/Corrections

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