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The pentapeptide Gly-Thr-Gly-Lys-Thr confers sensitivity to anti-cancer drugs by inhibition of CAGE binding to GSK3 beta and decreasing the expression of cyclinD1

Title
The pentapeptide Gly-Thr-Gly-Lys-Thr confers sensitivity to anti-cancer drugs by inhibition of CAGE binding to GSK3 beta and decreasing the expression of cyclinD1
Authors
Kim, YoungmiKim, HyunaPark, DeokbumLee, HansooLee, Yun SilChoe, JongseonKim, Young MyeongJeon, DoyongJeoung, Dooil
Ewha Authors
이윤실
SCOPUS Author ID
이윤실scopus
Issue Date
2017
Journal Title
ONCOTARGET
ISSN
1949-2553JCR Link
Citation
vol. 8, no. 8, pp. 13632 - 13651
Keywords
anti-cancer drug-resistanceCAGEcyclinD1GSK3 betapeptides
Publisher
IMPACT JOURNALS LLC
Indexed
SCIE; SCOPUS WOS
Abstract
We previously reported the role of cancer/testis antigen CAGE in the response to anti-cancer drugs. CAGE increased the expression of cyclinD1, and pGSK3 beta(Ser9), an inactive GSK3 beta, while decreasing the expression of phospho-cyclinD1Thr(286). CAGE showed binding to GSK3 beta and the domain of CAGE (amino acids 231-300) necessary for binding to GSK3 beta and for the expression regulation of cyclinD1 was determined. (269)GTGKT(273) peptide, corresponding to the DEAD box helicase domain of CAGE, decreased the expression of cyclinD1 and pGSK3 beta(Ser9) while increasing the expression of phosphocyclinD1(Thr286). GTGKT peptide showed the binding to CAGE and prevented CAGE from binding to GSK3 beta. GTGKT peptide changed the localization of CAGE and inhibited the binding of CAGE to the promoter sequences of cyclin D1. GTGKT peptide enhanced the apoptotic effects of anti-cancer drugs and decreased the migration, invasion, angiogenic, tumorigenic and metastatic potential of anti-cancer drug-resistant cancer cells. We found that Lys(272) of GTGKT peptide was necessary for conferring anti-cancer activity. Peptides corresponding to the DEAD box helicase domain of CAGE, such as AQTGTGKT, QTGTGKT and TGTGKT, also showed anti-cancer activity by preventing CAGE from binding to GSK3 beta. GTGKT peptide showed ex vivo tumor homing potential. Thus, peptides corresponding to the DEAD box helicase domain of CAGE can be developed as anti-cancer drugs in cancer patients expressing CAGE.
DOI
10.18632/oncotarget.14621
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약학대학 > 약학과 > Journal papers
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