Abstracts (poster) - Wissenschaft Online
Abstracts (poster) - Wissenschaft Online
Abstracts (poster) - Wissenschaft Online
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Andrea Felten, Peter Leister, Karl Heinz Scheidtmann<br />
Novel Coactivators of Androgen Receptor: AATF and ZIP<br />
Kinase<br />
The androgen receptor (AR) is a ligand-dependent transcription factor involved in<br />
differentiation, proliferation and homeostasis. The transcriptional activity of AR is<br />
mediated by interaction with multiple coactivators, which serve in chromatin modification<br />
or remodeling, or provide a link between specific and general transcription factors. We<br />
recently identified AATF (Apoptosis antagonizing transcription factor) and ZIP kinase<br />
(Zipper interacting protein kinase) as novel coactivators of the AR. Following hormone<br />
treatment, AR, AATF, and ZIP kinase formed physical complexes and associated with the<br />
promoter and enhancer of the prostate-specific antigen gene, as revealed by chromatin<br />
immunoprecipitation. AATF seems to serve as adaptor to facilitate or stabilize the<br />
interaction between AR and ZIP kinase while ZIP kinase exerts its function as a kinase.<br />
Significantly, depletion of ZIP kinase by siRNA reduced AR-mediated transactivation.<br />
However, neither AR nor AATF are phosphorylated by ZIP kinase in vitro suggesting that<br />
it phosphorylates other coactivators or chromatin proteins, particularly histones. Indeed,<br />
H3 is phosphorylated at Thr11 in the vicinity of the PSA enhancer. However, a role of ZIP<br />
kinase in this modification has to be established. Other candidate substrates of ZIP<br />
kinase are members of the p160 family, SRC1 and/or SRC3 which are heavily<br />
phosphorylated by different kinases and which form complexes with ZIP kinase. These<br />
issues are presently under investigation.<br />
Supported by DFG<br />
Literature<br />
Leister et al. (2003). Apoptosis Antagonizing Transcription Factor AATF is a novel coactivator<br />
of nuclear hormone receptors. Signal Transduction 3, 17-25.<br />
Leister et al. (2007). ZIP kinase plays a crucial role in androgen receptor-mediated<br />
transcription. Oncogene, 1–9<br />
contact:<br />
Prof Karl Heinz Scheidtmann<br />
University of Bonn<br />
Genetics<br />
kh.scheidtmann@uni-bonn.de<br />
Roemerstr. 164<br />
53177 Bonn (Germany)
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