| p27kip1 protein levels reflect a nexus of oncogenic signaling during cell transformation. | |
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MedLine Citation:
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PMID: 22511779 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Jeffrey P Miller; Nancy Yeh; Christoph P Hofstetter; Doruk Keskin; Andrew S Goldstein; Andrew Koff |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-04-17 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 287 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2012 Jun |
Date Detail:
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Created Date: 2012-06-11 Completed Date: 2012-09-21 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 19775-85 Citation Subset: IM |
Affiliation:
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Department of Molecular Biology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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CA89563/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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