The Short Isoform of the Ubiquitin Ligase NEDD4L Is a CREB Target Gene in Hepatocytes

摘要: During cycles of fasting and feeding, liver function is regulated by both transcriptional post-translational events. Regulated protein degradation has recently emerged as a key mechanism to control abundance specific hepatic proteins under different nutritional conditions. As glucagon signaling through cAMP PKA central glucose output during fasting, we hypothesized that this pathway may also regulate ubiquitin ligases in the fasted state. Here show stimuli promote expression short isoform E3 ligase Nedd4l primary mouse hepatocytes. Nedd4l-short mRNA NEDD4L (short isoform) accumulate glucagon-treated hepatocytes tissues fasting. We identified functional response element alternate promoter; mutation blunts cAMP-induced reporter construct. CREB occupies endogenous locus near element. its co-activator CRTC2, activated stimuli, contribute glucagon-stimulated siRNA-mediated depletion did not affect gluconeogenic gene expression, or glycogen synthesis. Our findings reveal new regulation cells.