Regulation der Funktion des Transkriptionsfaktors Stat5 durch O-Glykosylierung und Phosphorylierung
Zusammenfassung der Projektergebnisse
Signal transducer and activator of transcription 5 (Stat5), a latent cytoplasmic transcription factor, becomes activated by phosphorylation upon cytokine, hormone, and growth factor interactions with their appropriate receptors and induces the transcription of target genes. It plays crucial roles in principal cell fate decisions and regulates cell differentiation, development, proliferation, apoptosis and inflammation. It is active in the mammary gland, the liver, in hematopoietic cells and other organs and has pleiotropic functions depending on its activation pathway and its site of action. We derived transgenic mice in which the expression of a LacZ reporter gene is directed by Stat5 specific response elements and visualized the activation of Stat5 in cells of mouse organs at different developmental stages. The reporter gene activity reflects the timing and the location of Stat5 activation and was documented in mammary epithelial cells, granulocytes and macrophages of the transgenic lines.
Projektbezogene Publikationen (Auswahl)
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“Deregulation of Stat5 expression and activation causes mammary tumors in transgenic mice” International Journal of Cancer 112, 607-614 (2004)
E. Iavnilovitch, R.D. Cardiff, B. Groner and I. Barash
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“The coactivator CREB binding protein (CBP) interacts preferentially with the glycosylated form of the transcription factor Stat5” Journal of Biological Chemistry 279, 3563-3572 (2004)
C. Gewinner, G. Hart, N. Zachara, R. Cole, C. Beisenherz-Huss and B. Groner
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”Signal transducer and activator of transcription 5 (Stat5), a crucial regulator of immune and cancer cells” Current Drug Targets-Immune, Endocrine &Metabolic Disorders 5, 449-463 (2005)
Ilka Wittig and Bernd Groner
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“Expression of a carboxyl-terminally truncated Stat5, lacking a transactivation domain, in the mammary gland of transgenic mice inhibits cell proliferation during pregnancy, delays onset of milk secretion and enhances apoptosis upon involution” Molecular Reproduction and Development 73, 841-849 (2006)
E. Iavnilovitch, T. Eilon, B. Groner and I. Barash
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“The biological functions of the versatile transcription factors Stat3 and Stat5 and new strategies for their targeted inhibition” Journal of Mammary Gland Biology and Neoplasia 11, 75-87 (2006)
S. Desrivieres, C. Kunz, I. Barash, V. Vafaizadeh, C. Borghouts and B. Groner
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“Tumors caused by overexpression and forced activation of Stat5 in mammary epithelial cells of transgenic mice are parity dependent and develop post menopausal” International Journal of Cancer 121, 1892-1902 (2007)
T. Eilon, B. Groner and I. Barash
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“Heat shock protein 90 alpha, a prolactin-Stat5 target gene identified in breast cancer cells, is involved in apoptosis regulation” Breast Cancer Research, 10 (6), R94 (2008)
C. Perotti, R. Liu, C. Parusel, N. Böcher, J. Schultz, P. Bork, E. Pfitzner, B. Groner and C. Shemanko
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“The function of Stat3 in tumor cells and their microenvironment” Seminars in Cell and Developmental Biology 19, 341-350 (2008)
Bernd Groner, Peter Lucks and Corina Borghouts-Heinz
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“Genetically modified mammary stem cells define distinct roles for Stat5 in mammary gland development and breast cancer“ Stem Cells 28, 928-938 (2010)
V. Vafaizadeh, P. Klemmt, C. Brendel, C. Döbele, Kara Britt, W.H. Chen, P. Bork, B. Korn, S. Desrivieres and B. Groner
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“Visualisation of Stat3 and Stat5 transactivation activity with specific response element dependent reporter constructs integrated into lentiviral gene transfer vectors" Hormone Molecular Biology and Clinical Investigation 1, 127-138 (2010)
Katrin Gäbel, Nadja Lydia Bednorz, Corina Borghouts and Bernd Groner
