AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation

作者：Cianfanelli Valentina; Fuoco Claudia; Lorente Mar; Salazar Maria; Quondamatteo Fabio; Gherardini Pier Federico; De Zio Daniela; Nazio Francesca; Antonioli Manuela; D'Orazio Melania; Skobo Tatjana; Bordi Matteo; Rohde Mikkel; Dalla Valle Luisa; Helmer Citterich Manuela; Gretzmeier Christine; Dengjel Joern; Fimia Gian Maria; Piacentini Mauro; Di Bartolomeo Sabrina; Velasco Guillermo; Cecconi Francesco^*

来源：Nature Cell Biology, 2015, 17(1): 20-+.

DOI：10.1038/ncb3072

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.

• 出版日期2015-1