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.
%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
}