Mutual regulation between DNA-PKcs and snail1 leads to increased genomic instability and aggressive tumor characteristics
B-J Pyun ; H R Seo ; Y-S Lee ; J I Yook ; H W Nam ; H S Kim ; N H Kim ; E-J Kim ; Y B Jin ; H-J Lee
Cell Death & Disease, Vol.4(null) : e517, 2013
Cell Death & Disease
Although the roles of DNA-dependent protein kinase catalytic subunits (DNA-PKcs) in the non-homologous end joining (NHEJ) of DNA repair are well-recognized, the biological mechanisms and regulators by DNA-PKcs besides DNA repair, have not been clearly described. Here, we show that active DNA-PKcs caused by ionizing radiation, phosphorylated Snail1 at serine (Ser) 100, led to increased Snail1 stability. Furthermore, phosphorylated Snail1 at Ser100 reciprocally inhibited the kinase activity of DNA-PKcs, resulting in an inhibition of DNA repair activity. Moreover, Snail1 phosphorylation by DNA-PKcs was involved in genomic instability and aggressive tumor characteristics. Our results describe novel cellular mechanisms that affect genomic instability, sensitivity to DNA-damaging agents, and the migration of tumor cells by reciprocal regulation between DNA-PKcs and Snail1.