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

摘要: Inhibition of a main regulator cell metabolism, the protein kinase mTOR, induces autophagy and inhibits proliferation. However, molecular pathways involved in cross-talk between these two mTOR-dependent processes are largely unknown. Here we show that scaffold AMBRA1, member signalling network downstream target regulates proliferation by facilitating dephosphorylation degradation proto-oncogene c-Myc. We found AMBRA1 favours interaction c-Myc its phosphatase PP2A that, when mTOR is inhibited, it enhances activity on this specific target, thereby reducing division rate. As expected, such de-regulation correlates with increased tumorigenesis AMBRA1-defective systems, thus supporting role for as haploinsufficient tumour suppressor gene.