PD Dr. Anne Rascle
STAT5 signaling
Institut für Immunologie, Universität Regensburg F.-J.-Strauss-Allee 11 93042 Regensburg E-mail: anne.rascle@klinik.uni-regensburg.de Tel: +49 941 944 5467 Fax: +49-941-944-5462
Research interests
- Transcriptional regulation by the oncoprotein STAT5 in normal and cancer cells
Methods
- Standard molecular, cellular and biochemical approaches: cell culture, DNA, RNA and protein manipulation
- Gene expression studies: Quantitative RT-PCR, microarray-based expression profiling, luciferase reporter assays, RNA interference
- Chromatin and epigenetic studies: Chromatin Immunoprecipitation (ChIP, ChIP-on-chip), Chromatin remodeling (CHART-PCR)
Research overview
The signal transducer and activator of transcription STAT5 plays essential roles in regulating immune response, cell proliferation, differentiation and survival. STAT5 proteins normally reside as latent transcription factors in the cytoplasm of unstimulated cells. Following cytokine stimulation, STAT5 is phosphorylated by the JAK kinases, dimerizes, and is rapidly translocated into the nucleus where it binds to specific DNA binding sites and activates transcription of target genes (Fig.1). In normal cells, STAT5 activation is transient and tightly controlled.
Improper regulation, especially constitutive activation of STAT5, directly contributes to oncogenesis, and is associated to a variety of cancers (leukemia, mammary carcinoma, melanoma). We showed that deacetylase inhibitors can block STAT5 transcriptional activity, therefore validating their potential use for the treatment of STAT5-associated cancers. Our research aims at better characterizing STAT5 transcriptional activity, both in normal and cancer cells. Our current projects (Fig.1) focus on:
(i) Characterizing the molecular mechanism of STAT5 regulation by acetylation/deacetylation
(ii) Identifying compounds that can interfere - like deacetylase inhibitors - with STAT5 activity
(iii) Characterizing epigenetic alterations that are taking place upon STAT5 oncogenic activation
Team
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Lissy Besl, Technical Assistant (CBTA) |
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Susanne Brüggemann, Technical Assistant (MTLA) Tel: +49-941-944-5473 |
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Dominik Buob, Undergraduate |
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Sophia Schabel, PhD student Tel: +49-941-944-5473 |
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Samy Unser, PhD student Tel: +49-941-944-5473 |
Funding
Förderlinie C, University of Regensburg
ReForM Z, University Hospital Regensburg
Relevant publications
Basham, B., Sathe, M., Grein, J., McClanahan, T., d'Andrea, A., Lees, E., and Rascle, A.* (2008). In vivo Identification of Novel STAT5 Target Genes. Nucleic Acids Res. 36, 3802-18.
Burrows, J.F., McGrattan, M., Rascle, A., Humbert, M., Baek K-H., and Johnston, J.A. (2004). DUB-3, a cytokine-inducible deubiquitinating enzyme that blocks proliferation. J. Biol. Chem. 279, 13993-14000.
Nagalakshmi, M.L., Rascle, A., Zurawski, S., Menon, S., and de Waal Malefyt, R. (2004). Interleukin-22 activates STAT3 and induces IL-10 by colon epithelial cells. Int. Immunopharmacol. 4, 679-691.
Rascle, A.* , Johnston, J.A., and Amati, B. (2003). A deacetylase activity is required for recruitment of the basal transcription machinery and transactivation by STAT5. Mol. Cell. Biol. 23, 4162-4173.
Rascle, A.* , and Lees, E. (2003). Chromatin acetylation and remodeling at the Cis promoter during STAT5-induced transcription. Nucleic Acids Res. 31, 6882-6890.
Migone, T-S. § , Humbert, M. § , Rascle, A. § , Sanden, D., D'Andrea, A., and Johnston, J.A. (2001). The deubiquitinating enzyme Dub-2 prolongs cytokine-induced STAT activation and suppresses apoptosis following cytokine withdrawal. Blood 98, 1935-1941. § equal contribution
* corresponding author
Links:
Regensburg International Graduate School of Life Sciences ( RIGeL)