| First Author | Cianfanelli V | Year | 2015 |
| Journal | Nat Cell Biol | Volume | 17 |
| Issue | 1 | Pages | 20-30 |
| PubMed ID | 25438055 | Mgi Jnum | J:268220 |
| Mgi Id | MGI:6207125 | Doi | 10.1038/ncb3072 |
| Citation | Cianfanelli V, et al. (2015) AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation. Nat Cell Biol 17(1):20-30 |
| abstractText | Inhibition of a main regulator of cell metabolism, the protein kinase mTOR, induces autophagy and inhibits cell proliferation. However, the molecular pathways involved in the cross-talk between these two mTOR-dependent cell processes are largely unknown. Here we show that the scaffold protein AMBRA1, a member of the autophagy signalling network and a downstream target of mTOR, regulates cell proliferation by facilitating the dephosphorylation and degradation of the proto-oncogene c-Myc. We found that AMBRA1 favours the interaction between c-Myc and its phosphatase PP2A and that, when mTOR is inhibited, it enhances PP2A activity on this specific target, thereby reducing the cell division rate. As expected, such a de-regulation of c-Myc correlates with increased tumorigenesis in AMBRA1-defective systems, thus supporting a role for AMBRA1 as a haploinsufficient tumour suppressor gene. |
