NEURL4 regulates the transcriptional activity of tumor suppressor protein p53 by modulating its oligomerization

p53 is a transcription factor that regulates important cellular processes related to tumor suppression, including induction of senescence, apoptosis, and DNA repair as well as the inhibition of angiogenesis and cell migration. Therefore, it is critical to understand the molecular mechanism that regu...

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Autores: Cubillos Rojas, Mónica, Schneider, Taiane, Bartrons Bach, Ramon, Ventura Pujol, Francesc, Rosa López, José Luis
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/121161
Acesso em linha:https://hdl.handle.net/2445/121161
Access Level:acceso abierto
Palavra-chave:Proteïnes supressores de tumors
Oligòmers
Ubiqüitina
Transcripció genètica
Proliferació cel·lular
Tumor suppressor protein
Oligomers
Ubiquitin
Genetic transcription
Cell proliferation
id ES_09d4bd2314e7a0b6c5d232f731c3fb75
oai_identifier_str oai:recercat.cat:2445/121161
network_acronym_str ES
network_name_str España
repository_id_str
spelling NEURL4 regulates the transcriptional activity of tumor suppressor protein p53 by modulating its oligomerizationCubillos Rojas, MónicaSchneider, TaianeBartrons Bach, RamonVentura Pujol, FrancescRosa López, José LuisProteïnes supressores de tumorsOligòmersUbiqüitinaTranscripció genèticaProliferació cel·lularTumor suppressor proteinOligomersUbiquitinGenetic transcriptionCell proliferationp53 is a transcription factor that regulates important cellular processes related to tumor suppression, including induction of senescence, apoptosis, and DNA repair as well as the inhibition of angiogenesis and cell migration. Therefore, it is critical to understand the molecular mechanism that regulates it. p53 tetramerization is a key step in its activation process and the regulation of this oligomerization, an important control point. The E3 ubiquitin ligase HERC2 controls the p53 transcriptional activity by regulation of its oligomerization state. HERC2-interacting proteins such as the adaptor-like protein with six neuralized domains NEURL4 are also candidates to regulate p53 activity. Here, we demonstrate the existence of an interaction network between NEURL4, HERC2 and p53 proteins. We report a functional interaction between NEURL4 and p53, involving the C-terminal region of p53 and the neuralized domains 3 and 4 of NEURL4. Through this interaction, NEURL4 regulates the transcriptional activity of p53. Thus, NEURL4 depletion reduced the transcriptional activity whereas NEURL4 overexpression increased it. In both cases, p53 stability was not affected. Although NEURL4 may interact with p53 independently of the E3 ubiquitin ligase HERC2, we observed that both proteins are needed to regulate the transcriptional activity of p53. Clonogenic assays confirmed the functional relevance of this interaction observing a decrease in cell growth by NEURL4 overexpression correlated to the increase of cellular cycle inhibitor p21 by p53 activation. Under these conditions, NEURL4 activated p53 oligomerization. All these findings identify NEURL4 as a novel regulator of the p53's signaling.Impact Journals2018201820172018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion13 p.application/pdfhttps://hdl.handle.net/2445/121161Articles publicats en revistes (Ciències Fisiològiques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.18632/oncotarget.18699Oncotarget, 2017, vol. 8, num. 37, p. 61824-61836https://doi.org/10.18632/oncotarget.18699cc-by (c) Cubillos Rojas, Mónica et al., 2017http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1211612026-05-29T05:05:01Z
dc.title.none.fl_str_mv NEURL4 regulates the transcriptional activity of tumor suppressor protein p53 by modulating its oligomerization
title NEURL4 regulates the transcriptional activity of tumor suppressor protein p53 by modulating its oligomerization
spellingShingle NEURL4 regulates the transcriptional activity of tumor suppressor protein p53 by modulating its oligomerization
Cubillos Rojas, Mónica
Proteïnes supressores de tumors
Oligòmers
Ubiqüitina
Transcripció genètica
Proliferació cel·lular
Tumor suppressor protein
Oligomers
Ubiquitin
Genetic transcription
Cell proliferation
title_short NEURL4 regulates the transcriptional activity of tumor suppressor protein p53 by modulating its oligomerization
title_full NEURL4 regulates the transcriptional activity of tumor suppressor protein p53 by modulating its oligomerization
title_fullStr NEURL4 regulates the transcriptional activity of tumor suppressor protein p53 by modulating its oligomerization
title_full_unstemmed NEURL4 regulates the transcriptional activity of tumor suppressor protein p53 by modulating its oligomerization
title_sort NEURL4 regulates the transcriptional activity of tumor suppressor protein p53 by modulating its oligomerization
dc.creator.none.fl_str_mv Cubillos Rojas, Mónica
Schneider, Taiane
Bartrons Bach, Ramon
Ventura Pujol, Francesc
Rosa López, José Luis
author Cubillos Rojas, Mónica
author_facet Cubillos Rojas, Mónica
Schneider, Taiane
Bartrons Bach, Ramon
Ventura Pujol, Francesc
Rosa López, José Luis
author_role author
author2 Schneider, Taiane
Bartrons Bach, Ramon
Ventura Pujol, Francesc
Rosa López, José Luis
author2_role author
author
author
author
dc.subject.none.fl_str_mv Proteïnes supressores de tumors
Oligòmers
Ubiqüitina
Transcripció genètica
Proliferació cel·lular
Tumor suppressor protein
Oligomers
Ubiquitin
Genetic transcription
Cell proliferation
topic Proteïnes supressores de tumors
Oligòmers
Ubiqüitina
Transcripció genètica
Proliferació cel·lular
Tumor suppressor protein
Oligomers
Ubiquitin
Genetic transcription
Cell proliferation
description p53 is a transcription factor that regulates important cellular processes related to tumor suppression, including induction of senescence, apoptosis, and DNA repair as well as the inhibition of angiogenesis and cell migration. Therefore, it is critical to understand the molecular mechanism that regulates it. p53 tetramerization is a key step in its activation process and the regulation of this oligomerization, an important control point. The E3 ubiquitin ligase HERC2 controls the p53 transcriptional activity by regulation of its oligomerization state. HERC2-interacting proteins such as the adaptor-like protein with six neuralized domains NEURL4 are also candidates to regulate p53 activity. Here, we demonstrate the existence of an interaction network between NEURL4, HERC2 and p53 proteins. We report a functional interaction between NEURL4 and p53, involving the C-terminal region of p53 and the neuralized domains 3 and 4 of NEURL4. Through this interaction, NEURL4 regulates the transcriptional activity of p53. Thus, NEURL4 depletion reduced the transcriptional activity whereas NEURL4 overexpression increased it. In both cases, p53 stability was not affected. Although NEURL4 may interact with p53 independently of the E3 ubiquitin ligase HERC2, we observed that both proteins are needed to regulate the transcriptional activity of p53. Clonogenic assays confirmed the functional relevance of this interaction observing a decrease in cell growth by NEURL4 overexpression correlated to the increase of cellular cycle inhibitor p21 by p53 activation. Under these conditions, NEURL4 activated p53 oligomerization. All these findings identify NEURL4 as a novel regulator of the p53's signaling.
publishDate 2017
dc.date.none.fl_str_mv 2017
2018
2018
2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/121161
url https://hdl.handle.net/2445/121161
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.18632/oncotarget.18699
Oncotarget, 2017, vol. 8, num. 37, p. 61824-61836
https://doi.org/10.18632/oncotarget.18699
dc.rights.none.fl_str_mv cc-by (c) Cubillos Rojas, Mónica et al., 2017
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Cubillos Rojas, Mónica et al., 2017
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 13 p.
application/pdf
dc.publisher.none.fl_str_mv Impact Journals
publisher.none.fl_str_mv Impact Journals
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869403128722358272
score 15,198674

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