title: 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.
authors: College of Pharmacy, Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea.
authors: B-J
authors: BJ
authors: Pyun
authors: H R
authors: HR
authors: Seo
authors: H-J
authors: HJ
authors: Lee
authors: Y B
authors: YB
authors: Jin
authors: E-J
authors: EJ
authors: Kim
authors: N H
authors: NH
authors: Kim
authors: H S
authors: HS
authors: Kim
authors: H W
authors: HW
authors: Nam
authors: J I
authors: JI
authors: Yook
authors: Y-S
authors: YS
authors: Lee
mesh_terms: D045744:Cell Line, Tumor; D002869:Chromosome Aberrations / Q000528:radiation effects; D059766:DNA End-Joining Repair / Q000528:radiation effects; D051747:DNA-Activated Protein Kinase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D042822:Genomic Instability / Q000528:radiation effects; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D010766:Phosphorylation; D011485:Protein Binding; D055550:Protein Stability; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011839:Radiation, Ionizing; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D021122:Protein Subunits; D034741:RNA, Small Interfering; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051747:DNA-Activated Protein Kinase