Intrinsically disordered chromatin protein NUPR1 binds to the C-terminal region of Polycomb RING1B

10 p.-6 fig.

Detalles Bibliográficos
Autores: Santofimia-Castaño, Patricia, Rizzuti, Bruno, Pey, Ángel L., Soubeyran, Philippe, Vidal, Miguel, Urrutia, Raúl, Iovanna, Juan Lucio, Neira, José L.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/154590
Acceso en línea:http://hdl.handle.net/10261/154590
Access Level:acceso abierto
Palabra clave:IDP
NUPR1
Polycomb group
RING1B
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spelling Intrinsically disordered chromatin protein NUPR1 binds to the C-terminal region of Polycomb RING1BSantofimia-Castaño, PatriciaRizzuti, BrunoPey, Ángel L.Soubeyran, PhilippeVidal, MiguelUrrutia, RaúlIovanna, Juan LucioNeira, José L.IDPNUPR1Polycomb groupRING1B10 p.-6 fig.Intrinsically disordered proteins (IDPs) are ubiquitous in eukaryotes, and they are often associated with diseases in humans. The protein NUPR1 is a multifunctional IDP involved in chromatin remodeling and in the development and progression of pancreatic cancer; however, the details of such functions are unknown. Polycomb proteins are involved in specific transcriptional cascades and gene silencing. One of the proteins of the Polycomb complex is the Ring finger protein 1 (RING1). RING1 is related to aggressive tumor features in multiple cancer types. In this work we characterized the interaction between NUPR1 and the paralogue RING1B in vitro, in silico, and in cellulo. The interaction occurred through the C-terminal region of RING1B (C-RING1B), with an affinity in the low micromolar range (∼10 μM). The binding region of NUPR1, mapped by NMR, was a hydrophobic polypeptide patch at the 30s region of its sequence, as pinpointed by computational results and site-directed mutagenesis at Ala33. The association between C-RING1B and wild-type NUPR1 also occurred in cellulo as tested by protein ligation assays; this interaction is inhibited by trifluoperazine, a drug known to hamper binding of wild-type NUPR1 with other proteins. Furthermore, the Thr68Gln and Ala33Gln/Thr68Gln mutants had a reduction in the binding toward C-RING1B as shown by in vitro, in silico, and in cellulo studies. This is an example of a well-folded partner of NUPR1, because its other interacting proteins are also unfolded. We hypothesize that NUPR1 plays an active role in chromatin remodeling and carcinogenesis, together with Polycomb proteins.This work was supported by Spanish Ministry of Economy and Competitiveness Grants CTQ 2015-64445-R (to J.L.N.) and BIO2015-66426-R (to Á.L.P.); Spanish re- gional government Junta de Andalucía Grant P11-CTS-07187 (to Á.L.P.);La Ligue Contre le Cancer, INCa, Canceropole Provence-Alpes-Côtes d’Azur, Direction Générale de l’Offre de Soins (Sites de Recherche Intégrée sur le Cancer), and INSERM (J.L.I.); and Fundación Alfonso Martín-Escudero (P.S.-C.).Peer reviewedNational Academy of Sciences (U.S.)Ministerio de Economía y Competitividad (España)Junta de AndalucíaDirection générale de l'offre de soins (France)Fundación Alfonso Martín EscuderoConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201720172017info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/154590reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CTQ2015-64445-Rinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BIO2015-66426-Rhttp://dx.doi.org/10.1073/pnas.1619932114Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1545902026-05-22T06:33:51Z
dc.title.none.fl_str_mv Intrinsically disordered chromatin protein NUPR1 binds to the C-terminal region of Polycomb RING1B
title Intrinsically disordered chromatin protein NUPR1 binds to the C-terminal region of Polycomb RING1B
spellingShingle Intrinsically disordered chromatin protein NUPR1 binds to the C-terminal region of Polycomb RING1B
Santofimia-Castaño, Patricia
IDP
NUPR1
Polycomb group
RING1B
title_short Intrinsically disordered chromatin protein NUPR1 binds to the C-terminal region of Polycomb RING1B
title_full Intrinsically disordered chromatin protein NUPR1 binds to the C-terminal region of Polycomb RING1B
title_fullStr Intrinsically disordered chromatin protein NUPR1 binds to the C-terminal region of Polycomb RING1B
title_full_unstemmed Intrinsically disordered chromatin protein NUPR1 binds to the C-terminal region of Polycomb RING1B
title_sort Intrinsically disordered chromatin protein NUPR1 binds to the C-terminal region of Polycomb RING1B
dc.creator.none.fl_str_mv Santofimia-Castaño, Patricia
Rizzuti, Bruno
Pey, Ángel L.
Soubeyran, Philippe
Vidal, Miguel
Urrutia, Raúl
Iovanna, Juan Lucio
Neira, José L.
author Santofimia-Castaño, Patricia
author_facet Santofimia-Castaño, Patricia
Rizzuti, Bruno
Pey, Ángel L.
Soubeyran, Philippe
Vidal, Miguel
Urrutia, Raúl
Iovanna, Juan Lucio
Neira, José L.
author_role author
author2 Rizzuti, Bruno
Pey, Ángel L.
Soubeyran, Philippe
Vidal, Miguel
Urrutia, Raúl
Iovanna, Juan Lucio
Neira, José L.
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Junta de Andalucía
Direction générale de l'offre de soins (France)
Fundación Alfonso Martín Escudero
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv IDP
NUPR1
Polycomb group
RING1B
topic IDP
NUPR1
Polycomb group
RING1B
description 10 p.-6 fig.
publishDate 2017
dc.date.none.fl_str_mv 2017
2017
2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/154590
url http://hdl.handle.net/10261/154590
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CTQ2015-64445-R
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BIO2015-66426-R
http://dx.doi.org/10.1073/pnas.1619932114
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv National Academy of Sciences (U.S.)
publisher.none.fl_str_mv National Academy of Sciences (U.S.)
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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