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

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...

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Autores: Cianfanelli, Valentina, Fuoco, Claudia, Lorente Pérez, María Del Mar, Salazar Roa, María, 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 Díez, Guillermo, Cecconi, Francesco
Tipo de recurso: artículo
Fecha de publicación:2014
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/97936
Acceso en línea:https://hdl.handle.net/20.500.14352/97936
Access Level:acceso abierto
Palabra clave:616-006.04
Ambra
Autophagy
Bioquímica (Biología)
Oncología
2403 Bioquímica
3207 Patología
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oai_identifier_str oai:docta.ucm.es:20.500.14352/97936
network_acronym_str ES
network_name_str España
repository_id_str
spelling AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradationCianfanelli, ValentinaFuoco, ClaudiaLorente Pérez, María Del MarSalazar Roa, MaríaQuondamatteo, FabioGherardini, Pier FedericoDe Zio, DanielaNazio, FrancescaAntonioli, ManuelaD’Orazio, MelaniaSkobo, TatjanaBordi, MatteoRohde, MikkelDalla Valle, LuisaHelmer-Citterich, ManuelaGretzmeier, ChristineDengjel, JoernFimia, Gian MariaPiacentini, MauroDi Bartolomeo, SabrinaVelasco Díez, GuillermoCecconi, Francesco616-006.04AmbraAutophagyBioquímica (Biología)Oncología2403 Bioquímica3207 PatologíaInhibition 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.Nature ResearchCecconi, FrancescoUniversidad Complutense de Madrid20142014-01-0120142014-01-01journal articlehttp://purl.org/coar/resource_type/c_6501AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/97936reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/979362026-06-02T12:44:21Z
dc.title.none.fl_str_mv AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation
title AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation
spellingShingle AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation
Cianfanelli, Valentina
616-006.04
Ambra
Autophagy
Bioquímica (Biología)
Oncología
2403 Bioquímica
3207 Patología
title_short AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation
title_full AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation
title_fullStr AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation
title_full_unstemmed AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation
title_sort AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation
dc.creator.none.fl_str_mv Cianfanelli, Valentina
Fuoco, Claudia
Lorente Pérez, María Del Mar
Salazar Roa, María
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 Díez, Guillermo
Cecconi, Francesco
author Cianfanelli, Valentina
author_facet Cianfanelli, Valentina
Fuoco, Claudia
Lorente Pérez, María Del Mar
Salazar Roa, María
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 Díez, Guillermo
Cecconi, Francesco
author_role author
author2 Fuoco, Claudia
Lorente Pérez, María Del Mar
Salazar Roa, María
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 Díez, Guillermo
Cecconi, Francesco
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Cecconi, Francesco
Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 616-006.04
Ambra
Autophagy
Bioquímica (Biología)
Oncología
2403 Bioquímica
3207 Patología
topic 616-006.04
Ambra
Autophagy
Bioquímica (Biología)
Oncología
2403 Bioquímica
3207 Patología
description 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.
publishDate 2014
dc.date.none.fl_str_mv 2014
2014-01-01
2014
2014-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/97936
url https://hdl.handle.net/20.500.14352/97936
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869413109925412864
score 15.81155

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