期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 527, 期 -, 页码 -出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2021.111240
关键词
Candidate plasticity gene 16; Jun dimerization protein 2; Protein kinase; Insulin; Diabetes; Glucotoxicity
资金
- Kagawa University Research Promotion Program (KURPP)
- Japan Society for the Promotion of Science [18K06134]
- Grants-in-Aid for Scientific Research [18K06134] Funding Source: KAKEN
The study found that CPG16 inhibits the expression of the insulin gene by phosphorylating JDP2, thus blocking the upregulation of insulin promoter activity by JDP2.
Chronic hyperglycemia causes pancreatic beta-cell dysfunction, impaired insulin secretion and the suppression of insulin gene expression. This phenomenon is referred to as glucotoxicity, and is a critical component of the pathogenesis of type 2 diabetes. We previously reported that the expression of candidate plasticity gene 16 (CPG16) was higher in rat pancreatic INS-1 beta-cells under glucotoxic conditions and CPG16 suppressed insulin promoter activity. However, the molecular mechanisms of the CPG16-mediated suppression of insulin gene expression are unclear. In this study, we found that CPG16 directly bound and phosphorylated jun dimerization protein 2 (JDP2), an AP-1 family transcription factor. CPG16 co-localized with JDP2 in the nucleus of INS-1 cells. JDP2 bound to the G1 element of the insulin promoter and up-regulated promoter activity. Finally, CPG16 suppressed the up-regulation of insulin promoter activity by JDP2 in a kinase activity-dependent manner. These results suggest that CPG16 suppresses insulin promoter activity by phosphorylating JDP2.
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