Abstract

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.

Autore Pugliese

• Fimia Gian Maria

Tutti gli autori

• Cianfanelli V. , Fuoco C. , Lorente M. , Salazar M. , Quondamatteo F. , Gherardini P.F. , De Zio D. , Nazio F. , Antonioli M. , D'Orazio M. , Skobo T. , Bordi M. , Rohde M. , Dalla Valle L. , Helmer-Citterich M. , Gretzmeier C. , Dengjel J. , Fimia G.M. , Piacentini M. , Di Bartolomeo S. , Velasco G. , Cecconi F.

Titolo volume/Rivista

NATURE CELL BIOLOGY

Anno di pubblicazione

2015

ISSN

1465-7392

ISBN

Non Disponibile

Numero di citazioni Wos

48

Ultimo Aggiornamento Citazioni

25/04/2018

Numero di citazioni Scopus

51

Ultimo Aggiornamento Citazioni

26/04/2018

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile