p53-mediated transcriptional regulation and activation of the actin cytoskeleton regulatory RhoC to LIMK2 signaling pathway promotes cell survival

摘要: The central arbiter of cell fate in response to DNA damage is p53, which regulates the expression genes involved cycle arrest, survival and apoptosis. Although many responses initiated by have been characterized, role actin cytoskeleton regulators largely unknown. We now show that RhoC LIM kinase 2 (LIMK2) are direct p53 target induced genotoxic agents. LIMK2 well-established roles regulation, our results indicate activation also has a pro-survival function following damage. LIMK inhibition siRNA-mediated knockdown or selective pharmacological blockade sensitized cells radio- chemotherapy, such treatments were sub-lethal when administered singly resulted death combined with inhibition. Our findings suggest combining inhibitors therapies could be more efficacious than single-agent administration, highlight novel connection between damage-induced mechanisms.