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Institute for Experimental Cancer Research Tumor Biology Center D-79106 Freiburg, Germany
Stat5 was discovered as a PRL-induced member of the Stat (signal transducer and activator of transcription) family. Its induction by many other cytokines and interleukins suggests that Stat5 plays a crucial role not only in mammary epithelial, but also in hematopoietic cells. Cell type- and promoter- specific functions of Stat5 are most likely modulated by the interaction with other transcription factors. We recently showed cross-talk between Stat5 and the glucocorticoid receptor. The activated glucocorticoid receptor forms a complex with Stat5 and enhances Stat5-mediated transcriptional induction. Conversely, Stat5 diminishes the induction of glucocorticoid-responsive genes. Here, we investigated the role of p300/CBP(CREB-binding protein), a transcriptional coactivator of several groups of transcription factors, in Stat5-mediated transactivation and in the cross-talk between Stat5 and the glucocorticoid receptor. p300/CBP acts as a coactivator of Stat5. Its ectopic expression enhances PRL-induced Stat5-mediated transcriptional activation. Consistent with this observation, we find that the adenovirus E1A protein, which binds to p300/CBP, suppresses Stat5-induced transcriptional activation. This inhibition requires the Stat5 transactivation domain and the p300/CBP binding site of E1A. Coimmunoprecipitation and mammalian two-hybrid assays demonstrate a direct interaction between the carboxyl-terminal transactivation domain of Stat5 and p300/CBP. p300/CBP also positively interacts with the glucocorticoid receptor and enhances glucocorticoid receptor-dependent transcriptional activation of the mouse mammary tumor virus-long terminal repeat promoter. Overexpression of p300/CBP does not counteract the Stat5-mediated inhibition of glucocorticoid receptor-dependent transactivation, i.e. the repression of the glucocorticoid response by Stat5 is not a consequence of competition for limiting amounts of p300/CBP.
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S. Magne, S. Caron, M. Charon, M.-C. Rouyez, and I. Dusanter-Fourt STAT5 and Oct-1 Form a Stable Complex That Modulates Cyclin D1 Expression Mol. Cell. Biol., December 15, 2003; 23(24): 8934 - 8945. [Abstract] [Full Text] [PDF]
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C. M. Litterst, S. Kliem, D. Marilley, and E. Pfitzner NCoA-1/SRC-1 Is an Essential Coactivator of STAT5 That Binds to the FDL Motif in the {alpha}-Helical Region of the STAT5 Transactivation Domain J. Biol. Chem., November 14, 2003; 278(46): 45340 - 45351. [Abstract] [Full Text] [PDF]
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K. Paukku, J. Yang, and O. Silvennoinen Tudor and Nuclease-Like Domains Containing Protein p100 Function as Coactivators for Signal Transducer and Activator of Transcription 5 Mol. Endocrinol., September 1, 2003; 17(9): 1805 - 1814. [Abstract] [Full Text] [PDF]
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E. B. Kabotyanski and J. M. Rosen Signal Transduction Pathways Regulated by Prolactin and Src Result in Different Conformations of Activated Stat5b J. Biol. Chem., May 2, 2003; 278(19): 17218 - 17227. [Abstract] [Full Text] [PDF]
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C. M. Litterst and E. Pfitzner An LXXLL Motif in the Transactivation Domain of STAT6 Mediates Recruitment of NCoA-1/SRC-1 J. Biol. Chem., September 20, 2002; 277(39): 36052 - 36060. [Abstract] [Full Text] [PDF]
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Y. E. Timsit and D. S. Riddick Stimulation of Hepatic Signal Transducer and Activator of Transcription 5b by GH Is Not Altered by 3-Methylcholanthrene Endocrinology, September 1, 2002; 143(9): 3284 - 3294. [Abstract] [Full Text] [PDF]
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B. Peng, K. D. Sutherland, E. Y. M. Sum, M. Olayioye, S. Wittlin, T. K. Tang, G. J. Lindeman, and J. E. Visvader CPAP Is a Novel Stat5-Interacting Cofactor that Augments Stat5-Mediated Transcriptional Activity Mol. Endocrinol., September 1, 2002; 16(9): 2019 - 2033. [Abstract] [Full Text] [PDF]
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N. Chughtai, S. Schimchowitsch, J.-J. Lebrun, and S. Ali Prolactin Induces SHP-2 Association with Stat5, Nuclear Translocation, and Binding to the beta -Casein Gene Promoter in Mammary Cells J. Biol. Chem., August 16, 2002; 277(34): 31107 - 31114. [Abstract] [Full Text] [PDF]
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J.-L. Carsol, S. Gingras, and J. Simard Synergistic Action of Prolactin (PRL) and Androgen on PRL-Inducible Protein Gene Expression in Human Breast Cancer Cells: A Unique Model for Functional Cooperation between Signal Transducer and Activator of Transcription-5 and Androgen Receptor Mol. Endocrinol., July 1, 2002; 16(7): 1696 - 1710. [Abstract] [Full Text] [PDF]
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 A.-K. Boer, A. L. Drayer, H. Rui, and E. Vellenga Prostaglandin-E2 enhances EPO-mediated STAT5 transcriptional activity by serine phosphorylation of CREB Blood, June 28, 2002; 100(2): 467 - 473. [Abstract] [Full Text] [PDF]
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 M. A. Rycyzyn and C. V. Clevenger The intranuclear prolactin/cyclophilin B complex as a transcriptional inducer PNAS, May 14, 2002; 99(10): 6790 - 6795. [Abstract] [Full Text] [PDF]
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A. B. Maurer, C. Wichmann, A. Gross, H. Kunkel, T. Heinzel, M. Ruthardt, B. Groner, and M. Grez The Stat5-RARalpha fusion protein represses transcription and differentiation through interaction with a corepressor complex Blood, April 15, 2002; 99(8): 2647 - 2652. [Abstract] [Full Text] [PDF]
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S. Ray, C. T. Sherman, M. Lu, and A. R. Brasier Angiotensinogen Gene Expression Is Dependent on Signal Transducer and Activator of Transcription 3-Mediated p300/cAMP Response Element Binding Protein-Binding Protein Coactivator Recruitment and Histone Acetyltransferase Activity Mol. Endocrinol., April 1, 2002; 16(4): 824 - 836. [Abstract] [Full Text] [PDF]
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 A. Lehtonen, S. Matikainen, M. Miettinen, and I. Julkunen Granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced STAT5 activation and target-gene expression during human monocyte/macrophage differentiation J. Leukoc. Biol., March 1, 2002; 71(3): 511 - 519. [Abstract] [Full Text] [PDF]
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T. Nakamura, R. Ouchida, T. Kodama, T. Kawashima, Y. Makino, N. Yoshikawa, S. Watanabe, C. Morimoto, T. Kitamura, and H. Tanaka Cytokine Receptor Common beta Subunit-mediated STAT5 Activation Confers NF-kappa B Activation in Murine proB Cell Line Ba/F3 Cells J. Biol. Chem., February 15, 2002; 277(8): 6254 - 6265. [Abstract] [Full Text] [PDF]
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 T. L.-Y. Chang, A. Mosoian, R. Pine, M. E. Klotman, and J. P. Moore A Soluble Factor(s) Secreted from CD8+ T Lymphocytes Inhibits Human Immunodeficiency Virus Type 1 Replication through STAT1 Activation J. Virol., January 15, 2002; 76(2): 569 - 581. [Abstract] [Full Text] [PDF]
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S.-H. Park, H. Yamashita, H. Rui, and D. J. Waxman Serine Phosphorylation of GH-Activated Signal Transducer and Activator of Transcription 5a (STAT5a) and STAT5b: Impact on STAT5 Transcriptional Activity Mol. Endocrinol., December 1, 2001; 15(12): 2157 - 2171. [Abstract] [Full Text] [PDF]
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C. M. Litterst and E. Pfitzner Transcriptional Activation by STAT6 Requires the Direct Interaction with NCoA-1 J. Biol. Chem., November 30, 2001; 276(49): 45713 - 45721. [Abstract] [Full Text] [PDF]
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J. Schwartz Editorial: Pulsatile Hormone Patterns Governing Transcription Factor Function Endocrinology, November 1, 2001; 142(11): 4595 - 4598. [Full Text] [PDF]
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 E. Cazes, J. Giron-Michel, S. Baouz, C. Doucet, F. Cagnoni, S. Oddera, M. Korner, G. Dasic, R. Testi, B. Azzarone, et al. Novel Anti-inflammatory Effects of the Inhaled Corticosteroid Fluticasone Propionate During Lung Myofibroblastic Differentiation J. Immunol., November 1, 2001; 167(9): 5329 - 5337. [Abstract] [Full Text] [PDF]
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 L.-y. Yu-Lee Stimulation of interferon regulatory factor-1 by prolactin Lupus, October 1, 2001; 10(10): 691 - 699. [Abstract] [PDF]
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A. Biola, P. Lefebvre, M. Perrin-Wolff, M. Sturm, J. Bertoglio, and M. Pallardy Interleukin-2 Inhibits Glucocorticoid Receptor Transcriptional Activity through a Mechanism Involving STAT5 (Signal Transducer and Activator of Transcription 5) but Not AP-1 Mol. Endocrinol., July 1, 2001; 15(7): 1062 - 1076. [Abstract] [Full Text] [PDF]
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 J. Araya, M. Maruyama, K. Sassa, T. Fujita, R. Hayashi, S. Matsui, T. Kashii, N. Yamashita, E. Sugiyama, and M. Kobayashi Ionizing radiation enhances matrix metalloproteinase-2 production in human lung epithelial cells Am J Physiol Lung Cell Mol Physiol, January 1, 2001; 280(1): L30 - L38. [Abstract] [Full Text] [PDF]
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J. A. Hural, M. Kwan, G. Henkel, M. B. Hock, and M. A. Brown An Intron Transcriptional Enhancer Element Regulates IL-4 Gene Locus Accessibility in Mast Cells J. Immunol., September 15, 2000; 165(6): 3239 - 3249. [Abstract] [Full Text] [PDF]
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H. Favre-Young, F. Dif, F. Roussille, B. A. Demeneix, P. A. Kelly, M. Edery, and A. de Luze Cross-Talk between Signal Transducer and Activator of Transcription (Stat5) and Thyroid Hormone Receptor-{beta} 1 (TR{beta}1) Signaling Pathways Mol. Endocrinol., September 1, 2000; 14(9): 1411 - 1424. [Abstract] [Full Text]
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Q. Zhu, K. Gregg, M. Lozano, J. Liu, and J. P. Dudley CDP Is a Repressor of Mouse Mammary Tumor Virus Expression in the Mammary Gland J. Virol., July 15, 2000; 74(14): 6348 - 6357. [Abstract] [Full Text]
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 K. Dorshkind and N. D. Horseman The Roles of Prolactin, Growth Hormone, Insulin-Like Growth Factor-I, and Thyroid Hormones in Lymphocyte Development and Function: Insights from Genetic Models of Hormone and Hormone Receptor Deficiency Endocr. Rev., June 1, 2000; 21(3): 292 - 312. [Abstract] [Full Text]
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S. Aittomaki, M. Pesu, B. Groner, O. A. Janne, J. J. Palvimo, and O. Silvennoinen Cooperation Among Stat1, Glucocorticoid Receptor, and PU.1 in Transcriptional Activation of the High-Affinity Fc{gamma} Receptor I in Monocytes J. Immunol., June 1, 2000; 164(11): 5689 - 5697. [Abstract] [Full Text] [PDF]
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K. De Bosscher, W. Vanden Berghe, L. Vermeulen, S. Plaisance, E. Boone, and G. Haegeman Glucocorticoids repress NF-kappa B-driven genes by disturbing the interaction of p65 with the basal transcription machinery, irrespective of coactivator levels in the cell PNAS, April 11, 2000; 97(8): 3919 - 3924. [Abstract] [Full Text] [PDF]
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I. Beuvink, D. Hess, H. Flotow, J. Hofsteenge, B. Groner, and N. E. Hynes Stat5a Serine Phosphorylation. SERINE 779 IS CONSTITUTIVELY PHOSPHORYLATED IN THE MAMMARY GLAND, AND SERINE 725 PHOSPHORYLATION INFLUENCES PROLACTIN-STIMULATED IN VITRO DNA BINDING ACTIVITY J. Biol. Chem., March 31, 2000; 275(14): 10247 - 10255. [Abstract] [Full Text] [PDF]
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