Ivan Gout
Posters-Accepted Abstracts: Biol Syst Open Access
Ribosomal protein S6 kinase (S6K) is a member of the AGC family of Ser/Thr kinases which also includes PKA, PKB (Akt), PKCs etc. Biochemical and genetic studies in cell-based and animal models have provided evidence that S6K is a principal player in the regulation of cell growth, size and energy metabolism. Two major signal transduction pathways, phosphatidylinositide 3-kinases (PI3K) and mammalian target of rapamycin (mTOR), coordinate the activity of S6Ks in response to extracellular and intracellular stimuli, such as growth factors, mitogens, metabolites and nutrients. In an activate state, S6Ks translocate to discrete cellular compartments/multienzyme complexes, where they interact with and phosphorylate diverse substrates implicated in the regulation of translation, RNA processing, cytoskeletal rearrangement, cell growth and survival. A growing body of evidence links S6K signalling to various human pathologies, including diabetes, ageing and cancer. In mammalian cells, there are two isoforms of S6K, termed S6K1 and S6K2. The activity and subcellular localization of S6Ks are regulated by multiple S/T phosphorylations in response to diverse extracellular stimuli. Furthermore, acetylation and ubiquitination have been implicated in regulating the function of S6Ks. We have recently uncovered a novel mode of S6K activation, mediated by specific interaction with DNA. Data on molecular mechanisms underlying this regulatory event and its involvement in coordinating transcription, proliferation and cell survival, and in mediating chemoresistance to anti-cancer drugs will be presented.
