Authors: | Shen, Y.; Devgan, G.; Darnell, J. E. Jr; Bromberg, J. F. |
Article Title: | Constitutively activated Stat3 protects fibroblasts from serum withdrawal and UV-induced apoptosis and antagonizes the proapoptotic effects of activated Stat1 |
Abstract: | Stats1 and 3 (signal transducers and activators of transcription) can be activated simultaneously, although not necessarily to the same degree or duration, by the interaction of cells with the same polypeptide ligand (EGF, PDGF, or high concentrations of IL-6, for example). However, these two Stat proteins can mediate opposing effects on cell growth and survival. Stat1 activation slows growth and promotes apoptosis. In contrast, activated Stat3 can protect cells from apoptosis. Furthermore, a constitutively active form of Stat3, Stat3-C (bridged by S-S linkages between cysteines instead of phosphotyrosines) can induce cellular transformation of fibroblasts. We have determined that fibroblasts transformed by Stat3-C are more resistant to proapoptotic stimuli than nontransformed cells. Also, to examine the potential opposing roles in apoptosis of Stat1 and Stat3, we studied the cervical carcinoma-derived cell line, Me180, which undergoes Stat1-dependent, IFNγ-induced apoptosis. Me180 cells that express Stat3-C are protected against IFNγ-mediated apoptosis. |
Keywords: | signal transduction; controlled study; protein expression; dna-binding proteins; proto-oncogene proteins; nonhuman; animal cell; animals; mice; stat1 protein; stat3 protein; apoptosis; cancer cell culture; tumor cells, cultured; bcl-x protein; animalia; gamma interferon; cell transformation; uterine cervix cancer; rat; ligand; interleukin 6; fibroblast; fibroblasts; cell line, transformed; stat3 transcription factor; trans-activators; ultraviolet rays; cell interaction; proto-oncogene proteins c-bcl-2; 3t3 cells; growth inhibition; polypeptide; growth inhibitors; bcl-2-associated x protein; interferon type ii; culture media, serum-free; stat1 transcription factor; oncogene protein pp60(v-src); humans; priority journal; article |
Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
Volume: | 98 |
Issue: | 4 |
ISSN: | 0027-8424 |
Publisher: | National Academy of Sciences |
Date Published: | 2001-02-13 |
Start Page: | 1543 |
End Page: | 1548 |
Language: | English |
DOI: | 10.1073/pnas.041588198 |
PUBMED: | 11171987 |
PROVIDER: | scopus |
PMCID: | PMC29293 |
DOI/URL: | |
Notes: | Export Date: 21 May 2015 -- Source: Scopus |