NEDD4L limits cAMP signaling through ubiquitination of CREB-regulated transcription coactivator 3

What is it about?

CRTC is a transcription cofactor and in coordination with CREB regulates CREB target gene expression. There are three isoforms of CRTC in mammals. Aamong them, CRTC3 expresses in adipose tissues and in response to cAMP signal regulates lipolysis and energy expenditures. In this study, we found that NEDD4L ,through direct interaction with CRTC3, promotes ubiquitination and stability of CRTC3 protein. We showed that cAMP signal induces phosphorylation of NEDD4L at Ser 448 site and enhances binding to CRTC3. These results suggest that NEDD4L plays a key role in the feedback regulation of cAMP signaling by limiting CRTC3 protein levels. Because CRTC3 gene has been shown to be associated with human obesity, it is interesting to investigate whether NEDD4L plays a role in human obesity.

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