Publication Date:
1996-05-03
Description:
Signal transducers and activators of transcription (STAT) proteins can be conditionally activated in response to epidermal growth factor (EGF) and interferon (IFN)-gamma. STAT activation was correlated with cell growth inhibition in response to EGF and IFN-gamma. Activated STAT proteins specifically recognized the conserved STAT-responsive elements in the promoter of the gene encoding the cyclin-dependent kinase (CDK) inhibitor p21 WAF1/CIP1 and regulated the induction of p21 messenger RNA. IFN-gamma did not inhibit the growth of U3A cells, which are deficient in STAT1, but did inhibit the growth of U3A cells into which STAT1 alpha was reintroduced. Thus, STAT1 protein is essential for cell growth suppression in response to IFN-gamma. The STAT signaling pathway appears to negatively regulate the cell cycle by inducing CDK inhibitors in response to cytokines.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chin, Y E -- Kitagawa, M -- Su, W C -- You, Z H -- Iwamoto, Y -- Fu, X Y -- R01 AI34522/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1996 May 3;272(5262):719-22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Yale University School of Medicine, New Haven, CT 06520-8023, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8614832" target="_blank"〉PubMed〈/a〉
Keywords:
Base Sequence
;
Binding Sites
;
*Cell Division/drug effects
;
Cell Line
;
Cyclin-Dependent Kinase Inhibitor p21
;
Cyclins/biosynthesis/*genetics
;
DNA/biosynthesis
;
DNA-Binding Proteins/metabolism/*physiology
;
Epidermal Growth Factor/pharmacology
;
*Gene Expression Regulation
;
Humans
;
Interferon-gamma/pharmacology
;
Molecular Sequence Data
;
Promoter Regions, Genetic
;
RNA, Messenger/genetics/metabolism
;
STAT1 Transcription Factor
;
STAT3 Transcription Factor
;
*Signal Transduction
;
Trans-Activators/metabolism/*physiology
;
Transfection
;
Tumor Cells, Cultured
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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