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Mutual regulation between DNA-PKcs and Snail1 leads to increased genomic instability and aggressive tumor characteristics.

ABSTRACT: 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.

SUBMITTER: Pyun BJ

PROVIDER: S-EPMC3734834 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Mutual regulation between DNA-PKcs and Snail1 leads to increased genomic instability and aggressive tumor characteristics.

Pyun B-J BJ Seo H R HR Lee H-J HJ Jin Y B YB Kim E-J EJ Kim N H NH Kim H S HS Nam H W HW Yook J I JI Lee Y-S YS

Cell death & disease 20130228

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 ...[more]

PMID: 23449453

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