PD Dr. Anne Rascle

STAT5 signaling

research team funding publications links CV



As of May 2016, the STAT5 Signaling Research Group stopped its research activities.
Please direct any request to PD Dr. Anne Rascle,
Faculty of Biology and preclinical medicine, University of Regensburg

E-mail: anne.rascle@ur.de


Research overview BACK TO TOP


Signal transducer and activator of transcription STAT5 plays essential roles in regulating cell differentiation, proliferation and survival, as well as the immune response. STAT5 is normally activated by a number of cytokines (e.g., IL-2, IL-3), growth factors and hormones. Upon activation, STAT5 is phosphorylated by JAK kinases and is translocated into the nucleus where it activates the transcription of specific target genes (Cis, Osm, Bcl-x, c-Myc, …). While STAT5 activation is tightly controlled under physiological conditions, it is frequently aberrantly activated in a variety of cancers.

The STAT5 Signaling Research Group investigated the mechanism of transcriptional regulation by STAT5 in normal and cancer cells. A major focus was the identification and characterization of small-molecule inhibitors targeting STAT5 activity, thus potentially acting as cancer chemopreventive and/or chemotherapeutic agents.

Notably, we were the first to show that a class of anti-cancer agents, called deacetylase inhibitors, inhibit STAT5-mediated transcription (Rascle et al., 2003; Rascle and Lees, 2003). We recently demonstrated that deacetylase inhibitors block STAT5 activity by interfering with the function of the chromatin-associated factor Brd2, a member of the bromodomain and extra-terminal (BET) family essential for the proper recruitment of the transcriptional machinery (Pinz et al, 2015) (Figure A).

On the other hand, we identified synthetic chalcones (Pinz et al., 2014; Jobst et al., 2016; coll. with PD Dr. Sabine Amslinger, Organic Chemistry, Regensburg, Germany) and dietary isothiocyanates (sulforaphane, moringin; coll. with Prof. em. Renato Iori, CREA-CIN, Bologna, Italy; Pinz et al., 2014; Michl et al., 2016) as novel STAT5 inhibitors, targeting STAT5 signaling at various levels (Figures B, C).





AG Rascle in June 2013


Former lab members

Carina Michl, Graduate student (med.)
E-mail: carina.michl@stud.uni-regensburg.de

Sophia Pinz, Graduate student (Dr. rer. nat.)
(Dipl. Biochemist, Univ. Regensburg)
E-mail: sophia.pinz@klinik.uni-regensburg.de


Samy Unser, Graduate student (Dr. rer. nat.)
(Dipl. Biologist, Major in Human Genetics, Univ. Tübingen)
E-mail: samy.unser@klinik.uni-regensburg.de

Fabio Vivarelli, Visiting Ph.D. student
(Pharmacology and Toxicology)
University of Bologna, Italy

Julia Weigl, Master Thesis Biology

Belinda Jobst, Master Thesis Biology

Eva Kollmannsberger, Graduate student (med.)

Lissy Besl, Technical Assistant (CBTA)

Susanne Brüggemann, Technical Assistant (MTLA)

Kevin Niederquell, Undergraduate

Dominik Buob, Bachelor Thesis

Philipp Fischer, Undergraduate



Christina Seisenberger, Undergraduate

Krystina Beer, Undergraduate

Adrian Limmer, Undergraduate





Selected publications BACK TO TOP


Pinz, S., Unser, U., and Rascle, A.* (2016). Signal Transducer and Activator of Transcription STAT5 is recruited to c-Myc super-enhancer. BMC Mol. Biol. (in press).

Pinz, S., Unser, U., Buob, D., Fischer, P., Jobst, B., and Rascle, A.* (2015). Deacetylase inhibitors repress STAT5-mediated transcription by interfering with bromodomain and extra-terminal (BET) protein function. Nucleic Acids Res. 43, 3524-45.

Pinz, S., Unser, U., and Rascle, A.* (2014). The natural chemopreventive agent sulforaphane inhibits STAT5 activity. PLoS ONE 9(6): e99391.

Pinz, S., Unser, U., Brueggemann, S., Besl, E., Al-Rifai, N., Petkes, H., Amslinger, S.*, and Rascle, A.* (2014). The synthetic α-bromo-2’,3,4,4’-tetramethoxychalcone (α-Br-TMC) inhibits the JAK/STAT signaling pathway. PLoS ONE 9(3): e90275.

Rascle, A.*, Neumann, T., Raschta, A-S., Neumann, A., Heining, E., Kastner, J., and Witzgall, R.* (2009). The LIM-Homeodomain transcription factor LMX1B regulates expression of NF-kappa B target genes. Exp. Cell Res. 315, 76-96.

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.

Rascle, A.*, Johnston, J.A., and Amati, B. (2003). 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.

Rascle, A.*, Stowers R.S., Garza D., Lepesant J.A., and Hogness D.S. (2003). L63, the Drosophila PFTAIRE, interacts with two novel proteins unrelated to cyclins. Mech. Dev. 120, 617-628.

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

Rascle, A., Ferrand, N., Gandrillon, O., and Samarut, J. (1996). Myb-Ets fusion oncoprotein inhibits T3R/c-ErbA and RAR functions: a novel mechanism of action for leukemogenic transformation by E26 avian retrovirus. Mol. Cell. Biol. 16, 6338-6351.

Rascle, A., Ghysdael, J., and Samarut, J. (1994). c-ErbA, but not v-ErbA, interferes with a putative erythroid repressor for binding to the carbonic anhydrase II promoter. Oncogene 9, 2853-2867.

(*) corresponding author



Regensburg International Graduate School of Life Sciences ( RIGeL)

Publications (PubMed)