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

Cianfanelli, V. et al. (2015) AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation. Nature Cell Biology, 17(1), pp. 20-30. (doi:10.1038/ncb3072) (PMID:25438055) (PMCID:PMC4976803)

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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.

Item Type:Articles
Additional Information:There is an erratum associated with this item at Cianfanelli, V. et al. (2015) Corrigendum: AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation. Nature Cell Biology, 17(5), p. 706. (doi:10.1038/ncb3171) (PMID:25925585) http://eprints.gla.ac.uk/136903/
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Quondamatteo, Professor Fabio
Authors: 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., and Cecconi, F.
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Nature Cell Biology
Publisher:Nature Publishing Group
ISSN:1465-7392
ISSN (Online):1476-4679
Published Online:01 December 2014
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