Candidate plasticity gene 16 and jun dimerization protein 2 are involved in the suppression of insulin gene expression in rat pancreatic INS-1 β-cells
2021
Nakane, Tatsuto | Matsumoto, Suzuka | Iida, Satoshi | Ido, Ayae | Fukunaga, Kensaku | Murao, Koji | Sugiyama, Yasunori
Chronic hyperglycemia causes pancreatic β-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 β-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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