Mutual regulation between DNA-PKcs and snail1 leads to increased genomic instability and aggressive tumor characteristics |
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| Authors: | 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 |
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| Affiliation: | 1.College of Pharmacy, Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea;2.Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul, Korea;3.Department of Oral Pathology, College of Dentistry Yonsei University, Seoul, Korea;4.Korean Medicine-Based Herbal Drug Research Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine (KIOM), Daejeon, Korea |
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| 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. |
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| Keywords: | DNA-PKcs reciprocal regulation snail1 DNA repair snail1 phosphorylation |
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