Oleksandr Skorokhod1,3, Ganna Panasyuk1, Ivan Nemazanyy1, Ivan Gout1,2, Valeriy Filonenko1,3
1Department of Cell Signalling, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv;
2Department of Structural and Molecular Biology, University College London, United Kingdom;
3The State Key Laboratory of Molecular and Cellular Biology, Kyiv, Ukraine;
Ribosomal protein S6 kinases (S6Ks) are principal regulators of cell size, growth and metabolism. Signaling via the PI3K/mTOR pathway mediates the activation of S6Ks in response to various mitogenic stimuli, nutrients and stresses. To date, the regulation and cellular functions of S6Ks are not fully understood. Our aim was to investigate and characterize the interaction of S6Ks with the novel binding partner of S6Ks, Tudor domain containing 7 protein (TDRD7), which is a scaffold protein detected in complexes involved in the regulation of cytoskeleton dynamics, mRNA transport and translation, non-coding piRNAs processing and transposons silencing. This interaction was initially detected in the yeast two-hybrid screening of HeLa cDNA library and further confirmed by pull-down and co-immunoprecipitation assays. In addition we demonstrated that TDRD7 can form a complex with other isoform of S6K - S6K2. Notably, both isoforms of S6K were found to phosphorylate TDRD7 in vitro at multiple phosphorylation sites. Altogether, these findings demonstrate that TDRD7 is a novel substrate of S6Ks, suggesting the involvement of S6K signaling in the regulation of TDRD7 cellular functions.
Key words: S6K1, S6K2, TDRD7, Tudor domain, phosphorylation.
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© The Ukrainian Biochemical Journal