| First Author | Tai H | Year | 2017 |
| Journal | FASEB J | Volume | 31 |
| Issue | 10 | Pages | 4396-4406 |
| PubMed ID | 28626026 | Mgi Jnum | J:253321 |
| Mgi Id | MGI:6108508 | Doi | 10.1096/fj.201601159RR |
| Citation | Tai H, et al. (2017) Protein kinase Cbeta activates fat mass and obesity-associated protein by influencing its ubiquitin/proteasome degradation. FASEB J 31(10):4396-4406 |
| abstractText | Protein kinase Cbeta (PKCbeta) is a serine-threonine kinase associated with obesity and diabetic complications; its activation contributes to weight gain, and deletion of its gene results in resistance to genetic- and diet-induced obesity. Fat mass and obesity-associated (FTO) protein is a recently identified RNA demethylase, and its overexpression in mice leads to increased body weight as well as fat mass. Although sharing some features in anabolism regulation, PKCbeta and FTO have not been investigated together; therefore, their relationship has not been established. We report that PKCbeta positively regulates FTO on the posttranslation level, evidenced by the facts that PKCbeta activation contributes to high-glucose-induced FTO up-regulation, and overexpression of PKCbeta suppresses ubiquitin-proteasome degradation of FTO, whereas PKCbeta inactivation acts in the opposite manner. It was also found that PKCbeta can phosphorylate FTO on threonine, and this phosphorylation requires both catalytic and regulatory domains of PKCbeta. Moreover, PKCbeta inhibition can suppress 3T3-L1 cell differentiation in normal and FTO-overexpressing cells but not in FTO-silenced or -inhibited cells. We propose that PKCbeta acts to suppress the degradation of FTO protein and reveals the associated role of PKCbeta and FTO in adipogenesis, suggesting a new pathway that affects the development of obesity and metabolic diseases.-Tai, H., Wang, X., Zhou, J., Han, X., Fang, T., Gong, H., Huang, N., Chen, H., Qin, J., Yang, M., Wei, X., Yang, L., Xiao, H. Protein kinase Cbeta activates fat mass and obesity-associated protein by influencing its ubiquitin/proteasome degradation. |
