| First Author | Huber AL | Year | 2016 |
| Journal | Mol Cell | Volume | 64 |
| Issue | 4 | Pages | 774-789 |
| PubMed ID | 27840026 | Mgi Jnum | J:249123 |
| Mgi Id | MGI:6094647 | Doi | 10.1016/j.molcel.2016.10.012 |
| Citation | Huber AL, et al. (2016) CRY2 and FBXL3 Cooperatively Degrade c-MYC. Mol Cell 64(4):774-789 |
| abstractText | For many years, a connection between circadian clocks and cancer has been postulated. Here we describe an unexpected function for the circadian repressor CRY2 as a component of an FBXL3-containing E3 ligase that recruits T58-phosphorylated c-MYC for ubiquitylation. c-MYC is a critical regulator of cell proliferation; T58 is central in a phosphodegron long recognized as a hotspot for mutation in cancer. This site is also targeted by FBXW7, although the full machinery responsible for its turnover has remained obscure. CRY1 cannot substitute for CRY2 in promoting c-MYC degradation. Their unique functions may explain prior conflicting reports that have fueled uncertainty about the relationship between clocks and cancer. We demonstrate that c-MYC is a target of CRY2-dependent protein turnover, suggesting a molecular mechanism for circadian control of cell growth and a new paradigm for circadian protein degradation. |
