%0 Journal Article %1 Bromberg:1996:Proc-Natl-Acad-Sci-U-S-A:8755534 %A Bromberg, J F %A Horvath, C M %A Wen, Z %A Schreiber, R D %A Darnell, J E %D 1996 %J Proc Natl Acad Sci U S A %K stat1 transcriptionally %N 15 %P 7673-7678 %T Transcriptionally active Stat1 is required for the antiproliferative effects of both interferon alpha and interferon gamma %U http://www.ncbi.nlm.nih.gov/pmc/articles/PMC38805/ %V 93 %X 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 the Janus kinase-signal transducers and activators of transcription pathway, in which both IFN-alpha and IFN-gamma activate the transcription factor Stat1. A cell line lacking Stat1 (U3A) was not growth-arrested by IFN-alpha or IFN-gamma, and experiments were carried out with U3A cells permanently expressing normal or various mutant forms of Stat1 protein. Only cells in which complete Stat1 activity was available (Stat1alpha) were growth-inhibited by IFN-gamma. A mutant that supports 20-30% normal transcription did not cause growth restraint. In contrast, IFN-alpha growth restraint was imposed by cells producing Stat1beta, which lacks transcriptional activation potential. This parallels earlier results showing the truncated Stat1 can function in IFN-alpha gene activation. In addition to experiments on long-term cultured cells, we also found that wild-type primary mouse embryonic fibroblasts were inhibited by IFNs, but fibroblasts from Stat1-deficient mouse embryos were not inhibited by IFNs.

@article{Bromberg:1996:Proc-Natl-Acad-Sci-U-S-A:8755534, abstract = {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 the Janus kinase-signal transducers and activators of transcription pathway, in which both IFN-alpha and IFN-gamma activate the transcription factor Stat1. A cell line lacking Stat1 (U3A) was not growth-arrested by IFN-alpha or IFN-gamma, and experiments were carried out with U3A cells permanently expressing normal or various mutant forms of Stat1 protein. Only cells in which complete Stat1 activity was available (Stat1alpha) were growth-inhibited by IFN-gamma. A mutant that supports 20-30% normal transcription did not cause growth restraint. In contrast, IFN-alpha growth restraint was imposed by cells producing Stat1beta, which lacks transcriptional activation potential. This parallels earlier results showing the truncated Stat1 can function in IFN-alpha gene activation. In addition to experiments on long-term cultured cells, we also found that wild-type primary mouse embryonic fibroblasts were inhibited by IFNs, but fibroblasts from Stat1-deficient mouse embryos were not inhibited by IFNs.}, added-at = {2014-03-18T20:29:25.000+0100}, author = {Bromberg, J F and Horvath, C M and Wen, Z and Schreiber, R D and Darnell, J E}, biburl = {https://www.bibsonomy.org/bibtex/2d2a35c342965cb3cbce2e71c84286a8c/sagar87}, interhash = {fc7922ae9f0334b6a17bc194336a498b}, intrahash = {d2a35c342965cb3cbce2e71c84286a8c}, journal = {Proc Natl Acad Sci U S A}, keywords = {stat1 transcriptionally}, month = jul, number = 15, pages = {7673-7678}, pmid = {8755534}, timestamp = {2014-03-18T20:29:25.000+0100}, title = {Transcriptionally active Stat1 is required for the antiproliferative effects of both interferon alpha and interferon gamma}, url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC38805/}, volume = 93, year = 1996 }