Professor Yonsei University School of Medicine Seoul, Republic of Korea
Man-Wook Hur (Yonsei University School of Medicine)| Won-IL Choi (Yonse Univ Sch Med)
Zbtb7c is a proto-oncoprotein that control cell cycle, and glucose, glutamate, and lipid metabolism. Zbtb7c expression is increased in the liver and white adipose tissues of aging or high-fat diet-fed mice. The knockout or knockdown of the Zbtb7c gene expression decreases adipose tissues in aging mice and inhibits adipocyte differentiation in 3T3-L1 cells. We found that SIRT1 expression is derepressed in various tissues of Zbtb7c KO mice, and Zbtb7c is a potent transcription repressor of SIRT1. Mechanistically, Zbtb7c interacted with p53 and bound to the proximal promoter p53REs to repress the SIRT1 gene, in which p53RE2 is particularly critical. Zbtb7c made p53 interact with the corepressor mSin3A-HADC1 complex at the p53RE. By repressing the SIRT1 gene, Zbtb7c increased the acetylation of Pgc-1a and Pparg, which resulted in repression or activation of Pgc-1a or Pparg target genes of lipid metabolism. Our study provided a molecular target that can overexpress SIRT1 protein in the liver, pancreas, adipose tissues, which can be beneficial in the treatment of diabetes, obesity, longevity, etc.