Document Detail


Induction of p202, a modulator of apoptosis, during oncogenic transformation of NIH 3T3 cells by activated H-Ras (Q61L) contributes to cell survival.
MedLine Citation:
PMID:  12461788     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Previous studies have revealed that p202 (52 kDa), an interferon (IFN) and differentiation-inducible protein, negatively regulates cell proliferation and modulates cell survival. However, the role of p202 in transformed cells remains to be investigated. Here we report that constitutive expression of oncogenic H-Ras (Q61L) in NIH 3T3 cells, which resulted in cell transformation, was associated with increases in the steady-state levels of 202 RNA and protein. Interestingly, the increase in p202 levels in transformed cells correlated with increases in the activity of the transcription factor c-Jun/AP-1, which bound to the two potential AP-1 DNA binding sites (the AP-1CS1 and AP-1CS2) in the 5'-regulatory region of the 202 gene in gel mobility shift assays. Furthermore, the site-directed mutagenesis, coupled with promoter-reporter analyses, revealed that these two AP-1 DNA binding sites contribute to the regulation of the 202 gene in Ras transformed cells. Because treatment of transformed cells with a specific inhibitor of MEK (PD 98059) resulted in significant decreases in the levels of p202, these observations raise the possibility that in transformed cells Ras/Raf/MEK pathway regulates the transcriptional activation of the 202 gene. Significantly, decreases in the levels of p202 in Ras transformed NIH 3T3 cells under reduced serum conditions increased the susceptibility to apoptosis. Collectively, our observations support the idea that the transcriptional increases in the levels of p202 by oncogenic H-Ras in NIH 3T3 cells are needed for cell survival.
Authors:
Hong Xin; Yanbiao Geng; Rocky Pramanik; Divaker Choubey
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  88     ISSN:  0730-2312     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2003 Jan 
Date Detail:
Created Date:  2002-12-03     Completed Date:  2003-06-13     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  191-204     Citation Subset:  IM    
Copyright Information:
Copyright 2002 Wiley-Liss, Inc.
Affiliation:
Department of Radiation Oncology, Stritch School of Medicine, Loyola University Medical Center, 2160 South First Avenue, Building No. 1, Mail code: 114B, Maywood, IL 60153, USA.
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MeSH Terms
Descriptor/Qualifier:
3T3 Cells
Animals
Apoptosis*
Binding Sites
Blotting, Northern
Carrier Proteins / metabolism*
Cell Survival
Cell Transformation, Neoplastic*
Cytoplasm / metabolism
Flow Cytometry
Genes, Reporter
Genes, ras
Genetic Vectors
Immunoblotting
Intracellular Signaling Peptides and Proteins*
Mice
Mutagenesis, Site-Directed
Phosphoproteins / metabolism*
Plasmids / metabolism
Promoter Regions, Genetic
Proto-Oncogene Proteins p21(ras) / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Transfection
Grant Support
ID/Acronym/Agency:
CA69031/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Ifi202b protein, mouse; 0/Intracellular Signaling Peptides and Proteins; 0/Phosphoproteins; EC 3.6.5.2/Proto-Oncogene Proteins p21(ras)

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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