AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-MYC dephosphorylation and degradation
| Autor: | Cclaudia Fuoco, Daniela De Zio, Mikkel Rohde, María Salazar, Luisa Dalla Valle, Francesca Nazio, Valentina Cianfanelli, Mar Lorente, Matteo Bordi, Sabrina Di Bartolomeo, Mauro Piacentini, Manuela Antonioli, Fabio Quondamatteo, Francesco Cecconi, Guillermo Velasco, Gian Maria Fimia, Manuela Helmer-Citterich, Pier Federico Gherardini, Joern Dengjel, Christine Gretzmeier, Tatjana Skobo, Melania D'Orazio |
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| Přispěvatelé: | Cianfanelli, Valentina, Fuoco, Claudia, Lorente, Mar, Salazar, Maria, Quondamatteo, Fabio, Gherardini, Pier Federico, De Zio, Daniela, Nazio, Francesca, Antonioli, Manuela, D'Orazio, Melania, Skobo, Tatjana, Bordi, Matteo, Rohde, Mikkel, Dalla Valle, Luisa, Helmer Citterich, Manuela, Gretzmeier, Christine, Dengjel, Joern, Fimia, Gian Maria, Piacentini, Mauro, Di Bartolomeo, Sabrina, Velasco, Guillermo, Cecconi, Francesco |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Scaffold protein Cell division autophagy proliferation Ambra1 Haploinsufficiency Mice cell metabolism Genes Tumor Suppressor Protein Phosphatase 2 Phosphorylation RNA Small Interfering phosphatases Zebrafish mammalian autophagy Settore BIO/11 TOR Serine-Threonine Kinases inhibits autophagy Cell biology Cell Transformation Neoplastic regulates autophagy mTOR Female RNA Interference cell cycle Cell Division Settore BIO/06 protein phosphatase 2a growth Mice Transgenic Biology Article Proto-Oncogene Proteins c-myc Cell Line Tumor Autophagy Animals Humans cancer Protein kinase A PI3K/AKT/mTOR pathway Adaptor Proteins Signal Transducing Cell growth RPTOR association Cell Biology Protein phosphatase 2 Mice Inbred C57BL HEK293 Cells human malignancies pp2a HeLa Cells |
| Zdroj: | Nature cell biology Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid Consejería de Sanidad de la Comunidad de Madrid |
| ISSN: | 1476-4679 1465-7392 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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