TY - JOUR
T1 - Inhibition of snail1-DNA-PKcs protein-protein interface sensitizes cancer cells and inhibits tumor metastasis
AU - Kang, Ga Young
AU - Pyun, Bo Jeong
AU - Seo, Haeng Ran
AU - Jin, Yeung Bae
AU - Lee, Hae June
AU - Lee, Yoon Jin
AU - Lee, Yun Sil
PY - 2013/11/8
Y1 - 2013/11/8
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84887502836
U2 - 10.1074/jbc.M113.479840
DO - 10.1074/jbc.M113.479840
M3 - Article
C2 - 24085291
AN - SCOPUS:84887502836
SN - 0021-9258
VL - 288
SP - 32506
EP - 32516
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 45
ER -