Aurora kinase A mediated phosphorylation of mPOU is critical for skeletal muscle differentiation

Abstract

Aurora kinases are Ser/Thr-directed protein kinases which play pivotal roles in mitosis. Recent evidences highlight the importance of these kinases in non-mitotic biological events like skeletal myogenesis. Our earlier study identified POU6F1 (or mPOU) as a novel Aurora kinase A (AurkA) substrate. Here, we report that AurkA phosphorylates POU6F1 at Ser197 and inhibits its DNA binding ability. Delving into POU6F1 physiology, we find that the phospho-mimic (S197D) POU6F1 mutant exhibits enhancement, while wild type (WT) or phospho-deficient (S197A) mutant shows retardation in C2C12 myoblast differentiation. Interestingly, POU6F1 depletion phenocopies S197D-POU6F1 overexpression in the differentiation context. Collectively, our results signify mPOU as a negative regulator of skeletal muscle differentiation and strengthens the importance of AurkA in skeletal myogenesis.