Inhibition of Snail1-DNA-PKcs Protein-Protein Interface Sensitizes Cancer Cells and Inhibits Tumor Metastasis |
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| Authors: | Ga-Young Kang Bo-Jeong Pyun Haeng Ran Seo Yeung Bae Jin Hae-June Lee Yoon-Jin Lee Yun-Sil Lee |
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| Institution: | From the ‡College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750.;the §Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, and ;the ¶Korea Atomic Energy Research Institute, Advanced Radiation Technology Institute, Jeongeup-si, Jeollabuk-do 580-185, Korea |
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| Abstract: | Our previous study suggested that the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) interacts with Snail1, which affects genomic instability, sensitivity to DNA-damaging agents, and migration of tumor cells by reciprocal regulation between DNA-PKcs and Snail1. Here, we further investigate that a peptide containing 7-amino acid sequences (amino acids 15–21) of Snail1 (KPNYSEL, SP) inhibits the endogenous interaction between DNA-PKcs and Snail1 through primary interaction with DNA-PKcs. SP restored the inhibited DNA-PKcs repair activity and downstream pathways. On the other hand, DNA-PKcs-mediated phosphorylation of Snail1 was inhibited by SP, which resulted in decreased Snail1 stability and Snail1 functions. However, these phenomena were only shown in p53 wild-type cells, not in p53-defective cells. From these results, it is suggested that interfering with the protein interaction between DNA-PKcs and Snail1 might be an effective strategy for sensitizing cancer cells and inhibiting tumor migration, especially in both Snail1-overexpressing and DNA-PKcs-overexpressing cancer cells with functional p53. |
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| Keywords: | DNA Repair Migration p53 Peptides Phosphorylation DNA-PKcs Sensitization Snail1 Snail1 Phosphorylation |
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