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Science 3 May 1996:
Vol. 272. no. 5262, pp. 719 - 722
DOI: 10.1126/science.272.5262.719
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Reports

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 dagger

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 p21WAF1/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 STAT1alpha 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.

Department of Pathology, Yale University School of Medicine, New Haven, CT 06520-8023, USA.
* These authors contributed equally to this work.
dagger To whom correspondence should be addressed.


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Transforming growth factor beta 1 mediates cell-cycle arrest of primitive hematopoietic cells independent of p21Cip1/Waf1 or p27Kip1.
T. Cheng, H. Shen, N. Rodrigues, S. Stier, and D. T. Scadden (2001)
Blood 98, 3643-3649
   Abstract »    Full Text »    PDF »
Gas6 Induces Mesangial Cell Proliferation via Latent Transcription Factor STAT3.
M. Yanagita, H. Arai, T. Nakano, K. Ohashi, K. Mizuno, A. Fukatsu, T. Doi, and T. Kita (2001)
J. Biol. Chem. 276, 42364-42369
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A 36-Amino-Acid Region of CIITA Is an Effective Inhibitor of CBP: Novel Mechanism of Gamma Interferon-Mediated Suppression of Collagen {alpha}2(I) and Other Promoters.
X.-S. Zhu and J. P.-Y. Ting (2001)
Mol. Cell. Biol. 21, 7078-7088
   Abstract »    Full Text »    PDF »
Growth Factor Signaling in Cell Survival: Implications for Cancer Treatment.
S. Talapatra and C. B. Thompson (2001)
J. Pharmacol. Exp. Ther. 298, 873-878
   Abstract »    Full Text »
The Fanconi anemia complementation group C gene product: structural evidence of multifunctionality.
Q. Pang, T. A. Christianson, W. Keeble, J. Diaz, G. R. Faulkner, C. Reifsteck, S. Olson, and G. C. Bagby (2001)
Blood 98, 1392-1401
   Abstract »    Full Text »    PDF »
Interferon {gamma} inhibits growth of human pancreatic carcinoma cells via caspase-1 dependent induction of apoptosis.
K M Detjen, K Farwig, M Welzel, B Wiedenmann, and S Rosewicz (2001)
Gut 49, 251-262
   Abstract »    Full Text »    PDF »
Menstrual cycle-specific inhibition of endometrial stromal cell proliferation by oncostatin M.
Y. Ohata, T. Harada, A. Fujii, S. Yoshida, T. Iwabe, and N. Terakawa (2001)
Mol. Hum. Reprod. 7, 665-670
   Abstract »    Full Text »    PDF »
Combined Interferon-Alfa, 13-cis-Retinoic Acid, and Alpha-Tocopherol in Locally Advanced Head and Neck Squamous Cell Carcinoma: Novel Bioadjuvant Phase II Trial.
D. M. Shin, F. R. Khuri, B. Murphy, A. S. Garden, G. Clayman, M. Francisco, D. Liu, B. S. Glisson, L. Ginsberg, V. Papadimitrakopoulou, et al. (2001)
J. Clin. Oncol. 19, 3010-3017
   Abstract »    Full Text »    PDF »
Functional correction of FA-C cells with FANCC suppresses the expression of interferon {gamma}-inducible genes.
S. R. Fagerlie, J. Diaz, T. A. Christianson, K. McCartan, W. Keeble, G. R. Faulkner, and G. C. Bagby (2001)
Blood 97, 3017-3024
   Abstract »    Full Text »    PDF »
Interleukin-9 (IL-9) Induces Cell Growth Arrest Associated with Sustained Signal Transducer and Activator of Transcription Activation in Lymphoma Cells Overexpressing the IL-9 Receptor.
J.-B. Demoulin, J. Van Snick, and J.-C. Renauld (2001)
Cell Growth Differ. 12, 169-174
   Abstract »    Full Text »
Interferon-gamma downregulates ion transport in murine small intestine cultured in vitro.
D. Yoo, W. Lo, S. Goodman, W. Ali, C. Semrad, and M. Field (2000)
Am J Physiol Gastrointest Liver Physiol 279, G1323-G1332
   Abstract »    Full Text »    PDF »
Regulation of Fas Antigen (Fas, CD95)-Mediated Apoptosis of Bovine Granulosa Cells by Serum and Growth Factors.
S. M. Quirk, R. M. Harman, and R. G. Cowan (2000)
Biol Reprod 63, 1278-1284
   Abstract »    Full Text »
Phosphorylation-deficient Stat1 inhibits retinoic acid-induced differentiation and cell cycle arrest in U-937 monoblasts.
A. Dimberg, K. Nilsson, and F. Oberg (2000)
Blood 96, 2870-2878
   Abstract »    Full Text »    PDF »
Interferons: cell signalling, immune modulation, antiviral response and virus countermeasures.
S. Goodbourn, L. Didcock, and R. E. Randall (2000)
J. Gen. Virol. 81, 2341-2364
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Chronopharmacology of Antitumor Effect Induced by Interferon-beta in Tumor-Bearing Mice.
H. Takane, S. Ohdo, T. Yamada, E. Yukawa, and S. Higuchi (2000)
J. Pharmacol. Exp. Ther. 294, 746-752
   Abstract »    Full Text »
Nuclear Factor {{kappa}}B Subunits Induce Epithelial Cell Growth Arrest.
C. S. Seitz, H. Deng, K. Hinata, Q. Lin, and P. A. Khavari (2000)
Cancer Res. 60, 4085-4092
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Down-Regulation of neu/HER-2 by Interferon-{{gamma}} in Prostate Cancer Cells.
S. L. Kominsky, A. C. Hobeika, F. A. Lake, B. A. Torres, and H. M. Johnson (2000)
Cancer Res. 60, 3904-3908
   Abstract »    Full Text »
STAT5 Activation Is Required for Interleukin-9-dependent Growth and Transformation of Lymphoid Cells.
J.-B. Demoulin, C. Uyttenhove, D. Lejeune, A. Mui, B. Groner, and J.-C. Renauld (2000)
Cancer Res. 60, 3971-3977
   Abstract »    Full Text »
AP-1 and STAT mediate hyperoxia-induced gene transcription of heme oxygenase-1.
P. J. Lee, S. L. Camhi, B. Y. Chin, J. Alam, and A. M. K. Choi (2000)
Am J Physiol Lung Cell Mol Physiol 279, L175-L182
   Abstract »    Full Text »    PDF »
The Role of p21 in Interferon {{gamma}}-mediated Growth Inhibition of Human Breast Cancer Cells.
J. L. Gooch, R. E. Herrera, and D. Yee (2000)
Cell Growth Differ. 11, 335-342
   Abstract »    Full Text »
Regrowth of 5-Fluorouracil-treated Human Colon Cancer Cells Is Prevented by the Combination of Interferon {{gamma}}, Indomethacin, and Phenylbutyrate.
Y. Huang, C. M. Horvath, and S. Waxman (2000)
Cancer Res. 60, 3200-3206
   Abstract »    Full Text »


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