PUBLICATION
AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation
- 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., Cecconi, F.
- ID
- ZDB-PUB-170214-261
- Date
- 2015
- Source
- Nature cell biology 17: 20-30 (Journal)
- Registered Authors
- Dalla Valle, Luisa, Piacentini, Mauro, Skobo, Tatjana
- Keywords
- Cell proliferation, Cell signalling, Macroautophagy
- MeSH Terms
-
- Animals
- Female
- HEK293 Cells
- Cell Line, Tumor
- Phosphorylation
- Genes, Tumor Suppressor/physiology*
- RNA Interference
- Protein Phosphatase 2/metabolism
- Cell Division/genetics
- Proto-Oncogene Proteins c-myc/metabolism*
- Mice
- Male
- RNA, Small Interfering
- Autophagy/genetics*
- TOR Serine-Threonine Kinases/antagonists & inhibitors*
- HeLa Cells
- Zebrafish
- Haploinsufficiency*
- Mice, Transgenic
- Adaptor Proteins, Signal Transducing/genetics
- Adaptor Proteins, Signal Transducing/physiology*
- Cell Transformation, Neoplastic/genetics*
- Humans
- Mice, Inbred C57BL
- PubMed
- 25438055 Full text @ Nat. Cell Biol.
Citation
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. (2015) AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation. Nature cell biology. 17:20-30.
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.
Errata / Notes
This article is corrected by ZDB-PUB-220906-19.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
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Orthology
Engineered Foreign Genes
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