Caspase-2 is required for skeletal muscle differentiation and myogenesis

Publication date: Available online 29 July 2017
Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Author(s): K. Boonstra, D. Bloemberg, J. Quadrilatero
Caspase activation plays a crucial role in skeletal muscle differentiation. We previously found that caspase-2 activity increases during skeletal muscle cell differentiation; however, its direct effect on differentiation has not been fully investigated. Here, we found that caspase-2 activity transiently increased more than two-fold within 24h following induction of differentiation. Both pharmacological inhibition and shRNA-mediated knockdown of caspase-2 suppressed myogenic differentiation and dramatically impaired myotube formation. Furthermore, shRNA-mediated knockdown prevented induction of p21 and altered cell cycle profiles. Interestingly, caspase-3 activity was also dramatically reduced following caspase-2 inhibition or ablation. Moreover, caspase-2 and p21 were localized to the nucleus during early differentiation. Given the nuclear localization of caspase-2 and p21, as well as the impairment in p21 induction in caspase-2 knockdown cells, we propose that the role of caspase-2 is to regulate p21 induction at the onset of differentiation, which may regulate the myogenic program. Collectively, these results highlight a novel function for caspase-2 in myocyte differentiation and myogenesis.



from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2hep3kV
via IFTTT