Journal
NATURE CELL BIOLOGY
Volume 17, Issue 1, Pages 20-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb3072
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Funding
- KBVU [R72-A4408]
- Lundbeck Foundation [R167-2013-16100, R165-2013-15982]
- Novo Nordisk Foundation [7559]
- Bjarne Saxhof Foundation, AIRC [IG2010, IG2012]
- FISM
- Telethon Foundation [GGP10225]
- Italian Ministry of University and Research
- Italian Ministry of Health [RF 2009]
- Spanish Ministry of Economy and Competitiveness (MINECO) [PS09/01401, PI12/02248, FR2009-0052, IT2009-0053]
- Fundacion Mutua Madrilena [AP101042012]
- Lundbeck Foundation [R167-2013-16100, R165-2013-15982] Funding Source: researchfish
- Novo Nordisk Fonden [NNF13OC0007559] Funding Source: researchfish
- The Danish Cancer Society [R72-A4408] Funding Source: researchfish
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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.
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