TP53INP1, a tumor suppressor, interacts with LC3 and ATG8-family proteins through the LC3-interacting region (LIR) and promotes autophagy-dependent cell death

Autores
Seillier, M.; Peuget, S.; Gayet, O.; Gauthier, C.; N'Guessan, P.; Monte, Martin; Carrier, A.; Iovanna, J. L.; Dusetti, N. J.
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
TP53INP1 (tumor protein 53-induced nuclear protein 1) is a tumor suppressor, whose expression is downregulated in cancers from different organs. It was described as a p53 target gene involved in cell death, cell-cycle arrest and cellular migration. In this work, we show that TP53INP1 is also able to interact with ATG8-family proteins and to induce autophagy-dependent cell death. In agreement with this finding, we observe that TP53INP1, which is mainly nuclear, relocalizes in autophagosomes during autophagy where it is eventually degraded. TP53INP1-LC3 interaction occurs via a functional LC3-interacting region (LIR). Inactivating mutations of this sequence abolish TP53INP1-LC3 interaction, relocalize TP53INP1 in autophagosomes and decrease TP53INP1 ability to trigger cell death. Interestingly, TP53INP1 binds to ATG8-family proteins with higher affinity than p62, suggesting that it could partially displace p62 from autophagosomes, modifying thereby their composition. Moreover, silencing the expression of autophagy related genes (ATG5 or Beclin-1) or inhibiting caspase activity significantly decreases cell death induced by TP53INP1. These data indicate that cell death observed after TP53INP1-LC3 interaction depends on both autophagy and caspase activity. We conclude that TP53INP1 could act as a tumor suppressor by inducing cell death by caspase-dependent autophagy. © 2012 Macmillan Publishers Limited All rights reserved.
Fil: Seillier, M.. Inserm; Francia. Aix-Marseille Université; Francia
Fil: Peuget, S.. Inserm; Francia. Aix-Marseille Université; Francia
Fil: Gayet, O.. Inserm; Francia. Aix-Marseille Université; Francia
Fil: Gauthier, C.. Inserm; Francia. Aix-Marseille Université; Francia
Fil: N'Guessan, P.. Inserm; Francia. Aix-Marseille Université; Francia
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: Carrier, A.. Aix-Marseille Université; Francia. Inserm; Francia
Fil: Iovanna, J. L.. Aix-Marseille Université; Francia. Inserm; Francia
Fil: Dusetti, N. J.. Aix-Marseille Université; Francia. Inserm; Francia
Materia
Autophagy
Lc3
P53
P62
Tumor Suppressor
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:11336/60927
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/60927
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling TP53INP1, a tumor suppressor, interacts with LC3 and ATG8-family proteins through the LC3-interacting region (LIR) and promotes autophagy-dependent cell deathSeillier, M.Peuget, S.Gayet, O.Gauthier, C.N'Guessan, P.Monte, MartinCarrier, A.Iovanna, J. L.Dusetti, N. J.AutophagyLc3P53P62Tumor Suppressorhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1TP53INP1 (tumor protein 53-induced nuclear protein 1) is a tumor suppressor, whose expression is downregulated in cancers from different organs. It was described as a p53 target gene involved in cell death, cell-cycle arrest and cellular migration. In this work, we show that TP53INP1 is also able to interact with ATG8-family proteins and to induce autophagy-dependent cell death. In agreement with this finding, we observe that TP53INP1, which is mainly nuclear, relocalizes in autophagosomes during autophagy where it is eventually degraded. TP53INP1-LC3 interaction occurs via a functional LC3-interacting region (LIR). Inactivating mutations of this sequence abolish TP53INP1-LC3 interaction, relocalize TP53INP1 in autophagosomes and decrease TP53INP1 ability to trigger cell death. Interestingly, TP53INP1 binds to ATG8-family proteins with higher affinity than p62, suggesting that it could partially displace p62 from autophagosomes, modifying thereby their composition. Moreover, silencing the expression of autophagy related genes (ATG5 or Beclin-1) or inhibiting caspase activity significantly decreases cell death induced by TP53INP1. These data indicate that cell death observed after TP53INP1-LC3 interaction depends on both autophagy and caspase activity. We conclude that TP53INP1 could act as a tumor suppressor by inducing cell death by caspase-dependent autophagy. © 2012 Macmillan Publishers Limited All rights reserved.Fil: Seillier, M.. Inserm; Francia. Aix-Marseille Université; FranciaFil: Peuget, S.. Inserm; Francia. Aix-Marseille Université; FranciaFil: Gayet, O.. Inserm; Francia. Aix-Marseille Université; FranciaFil: Gauthier, C.. Inserm; Francia. Aix-Marseille Université; FranciaFil: N'Guessan, P.. Inserm; Francia. Aix-Marseille Université; FranciaFil: 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: Carrier, A.. Aix-Marseille Université; Francia. Inserm; FranciaFil: Iovanna, J. L.. Aix-Marseille Université; Francia. Inserm; FranciaFil: Dusetti, N. J.. Aix-Marseille Université; Francia. Inserm; FranciaNature Publishing Group2012-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/60927Seillier, M.; Peuget, S.; Gayet, O.; Gauthier, C.; N'Guessan, P.; et al.; TP53INP1, a tumor suppressor, interacts with LC3 and ATG8-family proteins through the LC3-interacting region (LIR) and promotes autophagy-dependent cell death; Nature Publishing Group; Cell Death and Differentiation; 19; 9; 9-2012; 1525-15351350-9047CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/cdd.2012.30info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/cdd201230info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:39:53Zoai:ri.conicet.gov.ar:11336/60927instacron: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:34982025-10-15 14:39:53.68CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv TP53INP1, a tumor suppressor, interacts with LC3 and ATG8-family proteins through the LC3-interacting region (LIR) and promotes autophagy-dependent cell death
title TP53INP1, a tumor suppressor, interacts with LC3 and ATG8-family proteins through the LC3-interacting region (LIR) and promotes autophagy-dependent cell death
spellingShingle TP53INP1, a tumor suppressor, interacts with LC3 and ATG8-family proteins through the LC3-interacting region (LIR) and promotes autophagy-dependent cell death
Seillier, M.
Autophagy
Lc3
P53
P62
Tumor Suppressor
title_short TP53INP1, a tumor suppressor, interacts with LC3 and ATG8-family proteins through the LC3-interacting region (LIR) and promotes autophagy-dependent cell death
title_full TP53INP1, a tumor suppressor, interacts with LC3 and ATG8-family proteins through the LC3-interacting region (LIR) and promotes autophagy-dependent cell death
title_fullStr TP53INP1, a tumor suppressor, interacts with LC3 and ATG8-family proteins through the LC3-interacting region (LIR) and promotes autophagy-dependent cell death
title_full_unstemmed TP53INP1, a tumor suppressor, interacts with LC3 and ATG8-family proteins through the LC3-interacting region (LIR) and promotes autophagy-dependent cell death
title_sort TP53INP1, a tumor suppressor, interacts with LC3 and ATG8-family proteins through the LC3-interacting region (LIR) and promotes autophagy-dependent cell death
dc.creator.none.fl_str_mv Seillier, M.
Peuget, S.
Gayet, O.
Gauthier, C.
N'Guessan, P.
Monte, Martin
Carrier, A.
Iovanna, J. L.
Dusetti, N. J.
author Seillier, M.
author_facet Seillier, M.
Peuget, S.
Gayet, O.
Gauthier, C.
N'Guessan, P.
Monte, Martin
Carrier, A.
Iovanna, J. L.
Dusetti, N. J.
author_role author
author2 Peuget, S.
Gayet, O.
Gauthier, C.
N'Guessan, P.
Monte, Martin
Carrier, A.
Iovanna, J. L.
Dusetti, N. J.
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Autophagy
Lc3
P53
P62
Tumor Suppressor
topic Autophagy
Lc3
P53
P62
Tumor Suppressor
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv TP53INP1 (tumor protein 53-induced nuclear protein 1) is a tumor suppressor, whose expression is downregulated in cancers from different organs. It was described as a p53 target gene involved in cell death, cell-cycle arrest and cellular migration. In this work, we show that TP53INP1 is also able to interact with ATG8-family proteins and to induce autophagy-dependent cell death. In agreement with this finding, we observe that TP53INP1, which is mainly nuclear, relocalizes in autophagosomes during autophagy where it is eventually degraded. TP53INP1-LC3 interaction occurs via a functional LC3-interacting region (LIR). Inactivating mutations of this sequence abolish TP53INP1-LC3 interaction, relocalize TP53INP1 in autophagosomes and decrease TP53INP1 ability to trigger cell death. Interestingly, TP53INP1 binds to ATG8-family proteins with higher affinity than p62, suggesting that it could partially displace p62 from autophagosomes, modifying thereby their composition. Moreover, silencing the expression of autophagy related genes (ATG5 or Beclin-1) or inhibiting caspase activity significantly decreases cell death induced by TP53INP1. These data indicate that cell death observed after TP53INP1-LC3 interaction depends on both autophagy and caspase activity. We conclude that TP53INP1 could act as a tumor suppressor by inducing cell death by caspase-dependent autophagy. © 2012 Macmillan Publishers Limited All rights reserved.
Fil: Seillier, M.. Inserm; Francia. Aix-Marseille Université; Francia
Fil: Peuget, S.. Inserm; Francia. Aix-Marseille Université; Francia
Fil: Gayet, O.. Inserm; Francia. Aix-Marseille Université; Francia
Fil: Gauthier, C.. Inserm; Francia. Aix-Marseille Université; Francia
Fil: N'Guessan, P.. Inserm; Francia. Aix-Marseille Université; Francia
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: Carrier, A.. Aix-Marseille Université; Francia. Inserm; Francia
Fil: Iovanna, J. L.. Aix-Marseille Université; Francia. Inserm; Francia
Fil: Dusetti, N. J.. Aix-Marseille Université; Francia. Inserm; Francia
description TP53INP1 (tumor protein 53-induced nuclear protein 1) is a tumor suppressor, whose expression is downregulated in cancers from different organs. It was described as a p53 target gene involved in cell death, cell-cycle arrest and cellular migration. In this work, we show that TP53INP1 is also able to interact with ATG8-family proteins and to induce autophagy-dependent cell death. In agreement with this finding, we observe that TP53INP1, which is mainly nuclear, relocalizes in autophagosomes during autophagy where it is eventually degraded. TP53INP1-LC3 interaction occurs via a functional LC3-interacting region (LIR). Inactivating mutations of this sequence abolish TP53INP1-LC3 interaction, relocalize TP53INP1 in autophagosomes and decrease TP53INP1 ability to trigger cell death. Interestingly, TP53INP1 binds to ATG8-family proteins with higher affinity than p62, suggesting that it could partially displace p62 from autophagosomes, modifying thereby their composition. Moreover, silencing the expression of autophagy related genes (ATG5 or Beclin-1) or inhibiting caspase activity significantly decreases cell death induced by TP53INP1. These data indicate that cell death observed after TP53INP1-LC3 interaction depends on both autophagy and caspase activity. We conclude that TP53INP1 could act as a tumor suppressor by inducing cell death by caspase-dependent autophagy. © 2012 Macmillan Publishers Limited All rights reserved.
publishDate 2012
dc.date.none.fl_str_mv 2012-09
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/11336/60927
Seillier, M.; Peuget, S.; Gayet, O.; Gauthier, C.; N'Guessan, P.; et al.; TP53INP1, a tumor suppressor, interacts with LC3 and ATG8-family proteins through the LC3-interacting region (LIR) and promotes autophagy-dependent cell death; Nature Publishing Group; Cell Death and Differentiation; 19; 9; 9-2012; 1525-1535
1350-9047
CONICET Digital
CONICET
url http://hdl.handle.net/11336/60927
identifier_str_mv Seillier, M.; Peuget, S.; Gayet, O.; Gauthier, C.; N'Guessan, P.; et al.; TP53INP1, a tumor suppressor, interacts with LC3 and ATG8-family proteins through the LC3-interacting region (LIR) and promotes autophagy-dependent cell death; Nature Publishing Group; Cell Death and Differentiation; 19; 9; 9-2012; 1525-1535
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.2012.30
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/cdd201230
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
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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score 13.22299

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