%0 Journal Article
%A Cianfanelli, Valentina
%A Fuoco, Claudia
%A Lorente Pérez, María Del Mar
%A Salazar Roa, María
%A Quondamatteo, Fabio
%A Gherardini, Pier Federico
%A De Zio, Daniela
%A Nazio, Francesca
%A Antonioli, Manuela
%A D’Orazio, Melania
%A Skobo, Tatjana
%A Bordi, Matteo
%A Rohde, Mikkel
%A Dalla Valle, Luisa
%A Helmer-Citterich, Manuela
%A Gretzmeier, Christine
%A Dengjel, Joern
%A Fimia, Gian Maria
%A Piacentini, Mauro
%A Di Bartolomeo, Sabrina
%A Velasco Díez, Guillermo
%A Cecconi, Francesco
%T AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation
%D 2014
%@ 1465-7392
%U https://hdl.handle.net/20.500.14352/97936
%X 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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