Transcriptionally active Stat1 is required for the antiproliferative effects of both interferon alpha and interferon gamma

作者: J. F. Bromberg , C. M. Horvath , Z. Wen , R. D. Schreiber , J. E. Darnell

DOI: 10.1073/PNAS.93.15.7673

关键词:

摘要: Type I (alpha, beta) and type II (gamma) interferons (IFNs) can restrict the growth of many cell types. INF-stimulated gene transcription, a key early event in IFN response, acts through Janus kinase-signal transducers activators transcription pathway, which both IFN-alpha IFN-gamma activate factor Stat1. A line lacking Stat1 (U3A) was not growth-arrested by or IFN-gamma, experiments were carried out with U3A cells permanently expressing normal various mutant forms protein. Only complete activity available (Stat1alpha) growth-inhibited IFN-gamma. that supports 20-30% did cause restraint. In contrast, restraint imposed producing Stat1beta, lacks transcriptional activation potential. This parallels earlier results showing truncated function activation. addition to on long-term cultured cells, we also found wild-type primary mouse embryonic fibroblasts inhibited IFNs, but from Stat1-deficient embryos IFNs.

参考文章(38)
M. Müller, C. Laxton, J. Briscoe, C. Schindler, T. Improta, J.E. Darnell, G.R. Stark, I.M. Kerr, Complementation of a mutant cell line : central role of the 91 kDa polypeptide of ISGF3 in the interferon-alpha and -gamma signal transduction pathways The EMBO Journal. ,vol. 12, pp. 4221- 4228 ,(1993) , 10.1002/J.1460-2075.1993.TB06106.X
K Polyak, J Y Kato, M J Solomon, C J Sherr, J Massague, J M Roberts, A Koff, p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest. Genes & Development. ,vol. 8, pp. 9- 22 ,(1994) , 10.1101/GAD.8.1.9
Yong Gu, Christoph W. Turck, David O. Morgan, Inhibition of CDK2 activity in vivo by an associated 20K regulatory subunit Nature. ,vol. 366, pp. 707- 710 ,(1993) , 10.1038/366707A0
S. Lin, T Kikuchi, W. Pledger, I Tamm, Interferon inhibits the establishment of competence in Go/S-phase transition. Science. ,vol. 233, pp. 356- 359 ,(1986) , 10.1126/SCIENCE.3726533
Chris Schindler, XIN-YUAN Fu, Teresa Improta, Ruedi Aebersold, James E Darnell Jr, Proteins of transcription factor ISGF-3: one gene encodes the 91-and 84-kDa ISGF-3 proteins that are activated by interferon alpha. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 89, pp. 7836- 7839 ,(1992) , 10.1073/PNAS.89.16.7836
R. McKendry, J. John, D. Flavell, M. Muller, I. M. Kerr, G. R. Stark, High-frequency mutagenesis of human cells and characterization of a mutant unresponsive to both alpha and gamma interferons Proceedings of the National Academy of Sciences of the United States of America. ,vol. 88, pp. 11455- 11459 ,(1991) , 10.1073/PNAS.88.24.11455
F. BALKWILL, J. TAYLOR-PAPADIMITRIOU, Interferon affects both G1 and S+G2 in cells stimulated from quiescence to growth. Nature. ,vol. 274, pp. 798- 800 ,(1978) , 10.1038/274798A0