Mirk/Dyrk1B mediates survival during the differentiation of C2C12 myoblasts.

摘要: Abstract The kinase Mirk/dyrk1B is essential for the differentiation of C2C12 myoblasts. Mirk reinforces G0/G1 arrest state in which occurs by directly phosphorylating and stabilizing p27Kip1 destabilizing cyclin D1. We now demonstrate that anti-apoptotic Knockdown endogenous RNA interference activated caspase 3 decreased myoblast survival 75%, whereas transient overexpression increased cell survival. exerts its effects during muscle at least part through on cycle inhibitor pro-survival molecule p21Cip1. Overexpression experiments demonstrated phosphorylates p21 within nuclear localization domain Ser-153 causing a portion typically to localize cytoplasm. Phosphomimetic GFP-p21-S153D was pancellular both cycling myoblasts NIH3T3 cells. Endogenous myotubes overexpressed cells were able cause wild-type GFP-p21 but not nonphosphorylatable mutant GFP-p21-S153A. Translocation cytoplasm enables block apoptosis inhibitory interaction with pro-apoptotic molecules. p21-S153D more effective than blocking activation 3. Transient expression also viability colony forming assays, p21-S153A had no effect. This Mirk-dependent change intracellular natural differentiation. localized exclusively nuclei proliferating found post-mitotic multinucleated adult human skeletal myofibers.