Projektergebnisse Regulation der Funktion des - gepris

Regulation der Funktion des Transkriptionsfaktors Stat5 durch O-Glykosylierung
und Phosphorylierung
Antragsteller:
Professor Dr. Bernd Groner
Georg-Speyer-Haus
Institut für Tumorbiologie und experimentelle Therapie
Paul-Ehrlich-Straße 42-44
60596 Frankfurt am Main
Telefon: +49 69 63395180
Telefax: +49 69 63395185
E-Mail: groner em.uni-frankfurt.de
Professor Dr. Horst Kunz
Johannes Gutenberg-Universität Mainz
Fachbereich Chemie, Pharmazie u Geowissenschaften
Institut für Organische Chemie
Duesbergweg 10-14
55128 Mainz
Telefon: +49 6131 3922334
Telefax: +49 6131 3924786
E-Mail: hokunz uni-mainz.de
Fachliche Zuordnung
Förderung
Zellbiologie
Förderung von 2005 bis 2010
Projektergebnisse
Erstellungsjahr
2009
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)
“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
“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
”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
“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
“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
“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
“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
“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
“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
“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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