MageA2 restrains cellular senescence by targeting the function of PMLIV/p53 axis at the PML-NBs

Autores
Peche, L. Y.; Scolz, M.; Ladelfa, Maria Fatima; Monte, Martin; Schneider, C.
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
MAGE-A genes are a subfamily of the melanoma antigen genes (MAGEs), whose expression is restricted to tumor cells of different origin and normal tissues of the human germline. Although the specific function of individual MAGE-A proteins is being currently explored, compelling evidence suggest their involvement in the regulation of different pathways during tumor progression. We have previously reported that MageA2 binds histone deacetylase (HDAC)3 and represses p53-dependent apoptosis in response to chemotherapeutic drugs. The promyelocytic leukemia (PML) tumor suppressor is a regulator of p53 acetylation and function in cellular senescence. Here, we demonstrate that MageA2 interferes with p53 acetylation at PML-nuclear bodies (NBs) and with PMLIV-dependent activation of p53. Moreover, a fraction of MageA2 colocalizes with PML-NBs through direct association with PML, and decreases PMLIV sumoylation through an HDAC-dependent mechanism. This reduction in PML post-translational modification promotes defects in PML-NBs formation. Remarkably, we show that in human fibroblasts expressing RasV12 oncogene, MageA2 expression decreases cellular senescence and increases proliferation. These results correlate with a reduction in NBs number and an impaired p53 response. All these data suggest that MageA2, in addition to its anti-apoptotic effect, could have a novel role in the early progression to malignancy by interfering with PML/p53 function, thereby blocking the senescence program, a critical barrier against cell transformation. © 2012 Macmillan Publishers Limited. All rights reserved.
Fil: Peche, L. Y.. Laboratorio Nazionale del Consorzio Interuniversitario per le Biotecnologie; Italia
Fil: Scolz, M.. Laboratorio Nazionale del Consorzio Interuniversitario per le Biotecnologie; Italia
Fil: Ladelfa, Maria Fatima. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Monte, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Schneider, C.. Laboratorio Nazionale del Consorzio Interuniversitario per le Biotecnologie; Italia. Università di Udine; Italia
Materia
Acetylation
Mage
P53
Pml
Senescence
Sumoylation
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/60923
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/60923
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling MageA2 restrains cellular senescence by targeting the function of PMLIV/p53 axis at the PML-NBsPeche, L. Y.Scolz, M.Ladelfa, Maria FatimaMonte, MartinSchneider, C.AcetylationMageP53PmlSenescenceSumoylationhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1MAGE-A genes are a subfamily of the melanoma antigen genes (MAGEs), whose expression is restricted to tumor cells of different origin and normal tissues of the human germline. Although the specific function of individual MAGE-A proteins is being currently explored, compelling evidence suggest their involvement in the regulation of different pathways during tumor progression. We have previously reported that MageA2 binds histone deacetylase (HDAC)3 and represses p53-dependent apoptosis in response to chemotherapeutic drugs. The promyelocytic leukemia (PML) tumor suppressor is a regulator of p53 acetylation and function in cellular senescence. Here, we demonstrate that MageA2 interferes with p53 acetylation at PML-nuclear bodies (NBs) and with PMLIV-dependent activation of p53. Moreover, a fraction of MageA2 colocalizes with PML-NBs through direct association with PML, and decreases PMLIV sumoylation through an HDAC-dependent mechanism. This reduction in PML post-translational modification promotes defects in PML-NBs formation. Remarkably, we show that in human fibroblasts expressing RasV12 oncogene, MageA2 expression decreases cellular senescence and increases proliferation. These results correlate with a reduction in NBs number and an impaired p53 response. All these data suggest that MageA2, in addition to its anti-apoptotic effect, could have a novel role in the early progression to malignancy by interfering with PML/p53 function, thereby blocking the senescence program, a critical barrier against cell transformation. © 2012 Macmillan Publishers Limited. All rights reserved.Fil: Peche, L. Y.. Laboratorio Nazionale del Consorzio Interuniversitario per le Biotecnologie; ItaliaFil: Scolz, M.. Laboratorio Nazionale del Consorzio Interuniversitario per le Biotecnologie; ItaliaFil: Ladelfa, Maria Fatima. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Monte, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Schneider, C.. Laboratorio Nazionale del Consorzio Interuniversitario per le Biotecnologie; Italia. Università di Udine; ItaliaNature Publishing Group2012-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/60923Peche, L. Y.; Scolz, M.; Ladelfa, Maria Fatima; Monte, Martin; Schneider, C.; MageA2 restrains cellular senescence by targeting the function of PMLIV/p53 axis at the PML-NBs; Nature Publishing Group; Cell Death and Differentiation; 19; 6; 6-2012; 926-9361350-9047CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/cdd.2011.173info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/cdd2011173info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:56:26Zoai:ri.conicet.gov.ar:11336/60923instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:56:27.032CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv MageA2 restrains cellular senescence by targeting the function of PMLIV/p53 axis at the PML-NBs
title MageA2 restrains cellular senescence by targeting the function of PMLIV/p53 axis at the PML-NBs
spellingShingle MageA2 restrains cellular senescence by targeting the function of PMLIV/p53 axis at the PML-NBs
Peche, L. Y.
Acetylation
Mage
P53
Pml
Senescence
Sumoylation
title_short MageA2 restrains cellular senescence by targeting the function of PMLIV/p53 axis at the PML-NBs
title_full MageA2 restrains cellular senescence by targeting the function of PMLIV/p53 axis at the PML-NBs
title_fullStr MageA2 restrains cellular senescence by targeting the function of PMLIV/p53 axis at the PML-NBs
title_full_unstemmed MageA2 restrains cellular senescence by targeting the function of PMLIV/p53 axis at the PML-NBs
title_sort MageA2 restrains cellular senescence by targeting the function of PMLIV/p53 axis at the PML-NBs
dc.creator.none.fl_str_mv Peche, L. Y.
Scolz, M.
Ladelfa, Maria Fatima
Monte, Martin
Schneider, C.
author Peche, L. Y.
author_facet Peche, L. Y.
Scolz, M.
Ladelfa, Maria Fatima
Monte, Martin
Schneider, C.
author_role author
author2 Scolz, M.
Ladelfa, Maria Fatima
Monte, Martin
Schneider, C.
author2_role author
author
author
author
dc.subject.none.fl_str_mv Acetylation
Mage
P53
Pml
Senescence
Sumoylation
topic Acetylation
Mage
P53
Pml
Senescence
Sumoylation
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv MAGE-A genes are a subfamily of the melanoma antigen genes (MAGEs), whose expression is restricted to tumor cells of different origin and normal tissues of the human germline. Although the specific function of individual MAGE-A proteins is being currently explored, compelling evidence suggest their involvement in the regulation of different pathways during tumor progression. We have previously reported that MageA2 binds histone deacetylase (HDAC)3 and represses p53-dependent apoptosis in response to chemotherapeutic drugs. The promyelocytic leukemia (PML) tumor suppressor is a regulator of p53 acetylation and function in cellular senescence. Here, we demonstrate that MageA2 interferes with p53 acetylation at PML-nuclear bodies (NBs) and with PMLIV-dependent activation of p53. Moreover, a fraction of MageA2 colocalizes with PML-NBs through direct association with PML, and decreases PMLIV sumoylation through an HDAC-dependent mechanism. This reduction in PML post-translational modification promotes defects in PML-NBs formation. Remarkably, we show that in human fibroblasts expressing RasV12 oncogene, MageA2 expression decreases cellular senescence and increases proliferation. These results correlate with a reduction in NBs number and an impaired p53 response. All these data suggest that MageA2, in addition to its anti-apoptotic effect, could have a novel role in the early progression to malignancy by interfering with PML/p53 function, thereby blocking the senescence program, a critical barrier against cell transformation. © 2012 Macmillan Publishers Limited. All rights reserved.
Fil: Peche, L. Y.. Laboratorio Nazionale del Consorzio Interuniversitario per le Biotecnologie; Italia
Fil: Scolz, M.. Laboratorio Nazionale del Consorzio Interuniversitario per le Biotecnologie; Italia
Fil: Ladelfa, Maria Fatima. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Monte, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Schneider, C.. Laboratorio Nazionale del Consorzio Interuniversitario per le Biotecnologie; Italia. Università di Udine; Italia
description MAGE-A genes are a subfamily of the melanoma antigen genes (MAGEs), whose expression is restricted to tumor cells of different origin and normal tissues of the human germline. Although the specific function of individual MAGE-A proteins is being currently explored, compelling evidence suggest their involvement in the regulation of different pathways during tumor progression. We have previously reported that MageA2 binds histone deacetylase (HDAC)3 and represses p53-dependent apoptosis in response to chemotherapeutic drugs. The promyelocytic leukemia (PML) tumor suppressor is a regulator of p53 acetylation and function in cellular senescence. Here, we demonstrate that MageA2 interferes with p53 acetylation at PML-nuclear bodies (NBs) and with PMLIV-dependent activation of p53. Moreover, a fraction of MageA2 colocalizes with PML-NBs through direct association with PML, and decreases PMLIV sumoylation through an HDAC-dependent mechanism. This reduction in PML post-translational modification promotes defects in PML-NBs formation. Remarkably, we show that in human fibroblasts expressing RasV12 oncogene, MageA2 expression decreases cellular senescence and increases proliferation. These results correlate with a reduction in NBs number and an impaired p53 response. All these data suggest that MageA2, in addition to its anti-apoptotic effect, could have a novel role in the early progression to malignancy by interfering with PML/p53 function, thereby blocking the senescence program, a critical barrier against cell transformation. © 2012 Macmillan Publishers Limited. All rights reserved.
publishDate 2012
dc.date.none.fl_str_mv 2012-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/60923
Peche, L. Y.; Scolz, M.; Ladelfa, Maria Fatima; Monte, Martin; Schneider, C.; MageA2 restrains cellular senescence by targeting the function of PMLIV/p53 axis at the PML-NBs; Nature Publishing Group; Cell Death and Differentiation; 19; 6; 6-2012; 926-936
1350-9047
CONICET Digital
CONICET
url http://hdl.handle.net/11336/60923
identifier_str_mv Peche, L. Y.; Scolz, M.; Ladelfa, Maria Fatima; Monte, Martin; Schneider, C.; MageA2 restrains cellular senescence by targeting the function of PMLIV/p53 axis at the PML-NBs; Nature Publishing Group; Cell Death and Differentiation; 19; 6; 6-2012; 926-936
1350-9047
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/cdd.2011.173
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/cdd2011173
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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