Cell Growth Arrest and Induction of Cyclin-Dependent Kinase
Inhibitor p21WAF1/CIP1 Mediated by STAT1
Yue E. Chin,
*
Motoo Kitagawa,
*
Wu-Chou S. Su,
Zhi-Hao You,
Yoshiki Iwamoto,
Xin-Yuan Fu
Signal transducers and activators of transcription (STAT)
proteins can be conditionally activated in response to epidermal growth
factor (EGF) and interferon (IFN)-
. STAT activation was correlated
with cell growth inhibition in response to EGF and IFN-
. Activated
STAT proteins specifically recognized the conserved STAT-responsive
elements in the promoter of the gene encoding the cyclin-dependent
kinase (CDK) inhibitor p21WAF1/CIP1 and regulated the
induction of p21 messenger RNA. IFN-
did not inhibit the growth of
U3A cells, which are deficient in STAT1, but did inhibit the growth of
U3A cells into which STAT1
was reintroduced. Thus, STAT1 protein is
essential for cell growth suppression in response to IFN-
. The STAT
signaling pathway appears to negatively regulate the cell cycle by
inducing CDK inhibitors in response to cytokines.
Department of Pathology, Yale University School of Medicine, New
Haven, CT 06520-8023, USA.
*
These authors contributed equally to this work.
To whom correspondence should be addressed.