| First Author | You JS | Year | 2018 |
| Journal | Sci Signal | Volume | 11 |
| Issue | 530 | PubMed ID | 29764991 |
| Mgi Jnum | J:284424 | Mgi Id | MGI:6381145 |
| Doi | 10.1126/scisignal.aao6847 | Citation | You JS, et al. (2018) A DGKzeta-FoxO-ubiquitin proteolytic axis controls fiber size during skeletal muscle remodeling. Sci Signal 11(530) |
| abstractText | Skeletal muscle rapidly remodels in response to various stresses, and the resulting changes in muscle mass profoundly influence our health and quality of life. We identified a diacylglycerol kinase zeta (DGKzeta)-mediated pathway that regulated muscle mass during remodeling. During mechanical overload, DGKzeta abundance was increased and required for effective hypertrophy. DGKzeta not only augmented anabolic responses but also suppressed ubiquitin-proteasome system (UPS)-dependent proteolysis. We found that DGKzeta inhibited the transcription factor FoxO that promotes the induction of the UPS. This function was mediated through a mechanism that was independent of kinase activity but dependent on the nuclear localization of DGKzeta. During denervation, DGKzeta abundance was also increased and was required for mitigating the activation of FoxO-UPS and the induction of atrophy. Conversely, overexpression of DGKzeta prevented fasting-induced atrophy. Therefore, DGKzeta is an inhibitor of the FoxO-UPS pathway, and interventions that increase its abundance could prevent muscle wasting. |
