Open AccessDown-regulation of the klf5-c-Myc interaction due to klf5 phosphorylation mediates resveratrol repressing the caveolin-1 transcription through the PI3K/PKD1/Akt pathway
Author(s) -
Hui Yang,
Qiuxia Chen,
Fangyun Sun,
Na Zhao,
LiRong Wen,
Li Lin,
Gai Ran
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0189156
Subject(s) - phosphorylation , resveratrol , pi3k/akt/mtor pathway , protein kinase b , transcription factor , caveolin 1 , transcription (linguistics) , promoter , chromatin immunoprecipitation , chemistry , hek 293 cells , biology , signal transduction , microbiology and biotechnology , cancer research , gene expression , biochemistry , gene , linguistics , philosophy
Resveratrol (RSV), a natural polyphenol, has been reported to produce effect on genes transcription in lipid metabolism. In this study, we aim to explore the novel mechanisms of RSV on the regulation of caveolin-1 (Cav-1) transcription. Via body weight, blood glucose, serum lipid, and liver pathology detection, we found that RSV decreased body weight, blood glucose and lipid accumulation in rats fed high-fat diet. Based on co-immunoprecipitation (Co-IP) and western blotting assay, we found that RSV up-regulated klf5 phosphorylation and decreased the interaction of klf5 with c-Myc, which were accompanied by down-regulation of Cav-1 expression in livers of rats fed with high-fat diet. Moreover, in HEK293 cells, we observed RSV enhanced klf5 phosphorylation and separated the interaction of klf5 with c-Myc through inhibiting the activation of PI3K/PKD1/Akt pathway, which maybe promoted c-Myc binding to the promoter to inhibit Cav-1 expression. The results of the present study demonstrated that RSV activated klf5 phosphorylation by inhibiting PI3K/PKD1/Akt pathway, and then attenuated the interaction of klf5 with c-Myc, subsequently probably promoted the c-Myc binding to the promoter to repress Cav-1 expression.