Mutual regulation between DNA-PKcs and snail1 leads to increased genomic instability and aggressive tumor characteristics

B. J. Pyun, H. R. Seo, H. J. Lee, Y. B. Jin, E. J. Kim, N. H. Kim, H. S. Kim, H. W. Nam, J. I. Yook, Y. S. Lee

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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 DNAPKcs, 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.

Original languageEnglish
JournalCell Death and Disease
Volume4
Issue number2
DOIs
StatePublished - Feb 2013

Keywords

  • DNA repair
  • DNA-PKcs
  • Reciprocal regulation
  • Snail1
  • Snail1 phosphorylation

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