p27 kip1 protein levels reflect a nexus of oncogenic signaling during cell transformation Journal Article
| Authors: | Miller, J. P.; Yeh, N.; Hofstetter, C. P.; Keskin, D.; Goldstein, A. S.; Koff, A. |
| Article Title: | p27 kip1 protein levels reflect a nexus of oncogenic signaling during cell transformation |
| Abstract: | 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.Wefound 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. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc. |
| Keywords: | signal transduction; controlled study; protein expression; protein phosphorylation; human cell; genetics; missense mutation; mutation, missense; nonhuman; protein function; cell proliferation; protein analysis; animal cell; mouse; animal; metabolism; animals; mice; amino acid substitution; protein degradation; cell line; animal experiment; animal model; protein stability; gene product; pathology; cell transformation, neoplastic; oncogene; antigens; protein purification; cell transformation; cyclin dependent kinase inhibitor 1b; cdkn1b protein, human; cyclin-dependent kinase inhibitor p27; carcinogenicity; protein dephosphorylation; amino acids; virus t antigen; antigens, polyomavirus transforming; protein determination; human cells; degradation; protein phosphatase 2a; tissue culture; cdkn1b protein, mouse; oncogenic viruses; protein phosphatase 2; protein level; proteolysis; virus small t antigen; cancer graft; oncoproteins; transforming activity; phosphoprotein phosphatase 2; arf1 gene; arf4 gene; arhgef2 gene; cdkn1b gene; csda gene; cyfip2 gene; gsk3a gene; herc5 gene; il1rap gene; iqgap2 gene; irak gene; loc643751 gene; pld1 gene; rap1a gene; rgl2 gene; rhoa gene; taf1b gene; tsc2 gene |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 287 |
| Issue: | 24 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2012-06-08 |
| Start Page: | 19775 |
| End Page: | 19785 |
| Language: | English |
| DOI: | 10.1074/jbc.M112.361972 |
| PROVIDER: | scopus |
| PMCID: | PMC3370163 |
| PUBMED: | 22511779 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 2 July 2012" - "CODEN: JBCHA" - "Source: Scopus" |
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