The intrinsically disordered, epigenetic factor RYBP binds to the citrullinating enzyme PADI4 in cancer cells

14 p.-6 fig.-1 tab.

Detalles Bibliográficos
Autores: Araujo-Abad, Salomé, Fuentes-Baile, María, Rizzuti, Bruno, Bazan, J. Fernando, Villamarin-Ortiz, Adrián, Saceda, Miguel, Fernández, Eduardo, Vidal, Miguel, Abian, Olga, Velázquez-Campoy, Adrián, de Juan Romero, Camino, Neira, José L.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:dnet:digitalcsic_::e52c895b645c76813d38e889a76640fa
Acceso en línea:http://hdl.handle.net/10261/336040
Access Level:acceso abierto
Palabra clave:Intrinsically disordered proteins
Protein-protein interactions
Fluorescence
Proximity ligation assay
Isothermal titration calorimetry
Citrullination
id ES_257550ccc042866c1961ae0366ab8f45
oai_identifier_str oai:dnet:digitalcsic_::e52c895b645c76813d38e889a76640fa
network_acronym_str ES
network_name_str España
repository_id_str
spelling The intrinsically disordered, epigenetic factor RYBP binds to the citrullinating enzyme PADI4 in cancer cellsAraujo-Abad, SaloméFuentes-Baile, MaríaRizzuti, BrunoBazan, J. FernandoVillamarin-Ortiz, AdriánSaceda, MiguelFernández, EduardoVidal, MiguelAbian, OlgaVelázquez-Campoy, Adriánde Juan Romero, CaminoNeira, José L.Intrinsically disordered proteinsProtein-protein interactionsFluorescenceProximity ligation assayIsothermal titration calorimetryCitrullination14 p.-6 fig.-1 tab.RYBP (Ring1 and YY 1 binding protein) is a multifunctional, intrinsically disordered protein (IDP), best described as a transcriptional regulator. It exhibits a ubiquitin-binding functionality, binds to other transcription factors, and has a key role during embryonic development. RYBP, which folds upon binding to DNA, has a Zn-finger domain at its N-terminal region. By contrast, PADI4 is a well-folded protein and it is one the human isoforms of a family of enzymes implicated in the conversion of arginine to citrulline. As both proteins intervene in signaling pathways related to cancer development and are found in the same localizations within the cell, we hypothesized they may interact. We observed their association in the nucleus and cytosol in several cancer cell lines, by using immunofluorescence (IF) and proximity ligation assays (PLAs). Binding also occurred in vitro, as measured by isothermal titration calorimetry (ITC) and fluorescence, with a low micromolar affinity (~1 μM). AlphaFold2-multimer (AF2) results indicate that PADI4's catalytic domain interacts with the Arg53 of RYBP docking into its active site. As RYBP sensitizes cells to PARP (Poly (ADP-ribose) polymerase) inhibitors, we applied them in combination with an enzymatic inhibitor of PADI4 observing a change in cell proliferation, and the hampering of the interaction of both proteins. This study unveils for the first time the possible citrullination of an IDP, and suggests that this new interaction, whether it involves or not citrullination of RYBP, might have implications in cancer development and progression.This research was funded by Ministry of Science and Innovation MCIN/AEI/10.13039/501100011033/ and “ERDF A way of Making Europe” [PID2021-127296OB-I00 to AVC; and PDC2022-133952-I00 to EF]; by Instituto de Salud Carlos III co-funded by European Social Fund “Investing in your future” [CP19/00095 to CdJ] [PI22/00824 to MS and CdJ] [PI18/00394 to OA]; by Diputación General de Aragón [“Protein targets and Bioactive Compounds group” E45-20R to AVC, and “Digestive Pathology Group” B25-20R to OA], and by Consellería de Innovación, Universidades, Ciencia y Sociedad Digital (Generalitat Valenciana) [CAICO 2021/0135 to CdJ and JLN].Peer reviewedElsevierMinisterio de Ciencia e Innovación (España)Instituto de Salud Carlos IIIDiputación General de AragónGeneralitat ValencianaAraujo-Abad, Salomé [0000-0001-7387-0363]Fuentes-Baile, María [0000-0003-3653-2407]Rizzuti, Bruno [0000-0003-1110-764X]Bazan, J. Fernando [0000-0002-3645-9935]Villamarin-Ortiz, Adrián [0000-0003-2768-9162]Saceda, Miguel [0000-0002-1564-3602]Vidal, Miguel [0000-0003-4374-6761]Abian, Olga [0000-0001-5664-1729]Velázquez-Campoy, Adrián [0000-0001-5702-4538]de Juan Romero, Camino [0000-0001-7890-8447]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202320232023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/336040reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.1016/j.ijbiomac.2023.125632Síinfo:eu-repo/semantics/openAccessoai:dnet:digitalcsic_::e52c895b645c76813d38e889a76640fa2026-05-22T06:33:51Z
dc.title.none.fl_str_mv The intrinsically disordered, epigenetic factor RYBP binds to the citrullinating enzyme PADI4 in cancer cells
title The intrinsically disordered, epigenetic factor RYBP binds to the citrullinating enzyme PADI4 in cancer cells
spellingShingle The intrinsically disordered, epigenetic factor RYBP binds to the citrullinating enzyme PADI4 in cancer cells
Araujo-Abad, Salomé
Intrinsically disordered proteins
Protein-protein interactions
Fluorescence
Proximity ligation assay
Isothermal titration calorimetry
Citrullination
title_short The intrinsically disordered, epigenetic factor RYBP binds to the citrullinating enzyme PADI4 in cancer cells
title_full The intrinsically disordered, epigenetic factor RYBP binds to the citrullinating enzyme PADI4 in cancer cells
title_fullStr The intrinsically disordered, epigenetic factor RYBP binds to the citrullinating enzyme PADI4 in cancer cells
title_full_unstemmed The intrinsically disordered, epigenetic factor RYBP binds to the citrullinating enzyme PADI4 in cancer cells
title_sort The intrinsically disordered, epigenetic factor RYBP binds to the citrullinating enzyme PADI4 in cancer cells
dc.creator.none.fl_str_mv Araujo-Abad, Salomé
Fuentes-Baile, María
Rizzuti, Bruno
Bazan, J. Fernando
Villamarin-Ortiz, Adrián
Saceda, Miguel
Fernández, Eduardo
Vidal, Miguel
Abian, Olga
Velázquez-Campoy, Adrián
de Juan Romero, Camino
Neira, José L.
author Araujo-Abad, Salomé
author_facet Araujo-Abad, Salomé
Fuentes-Baile, María
Rizzuti, Bruno
Bazan, J. Fernando
Villamarin-Ortiz, Adrián
Saceda, Miguel
Fernández, Eduardo
Vidal, Miguel
Abian, Olga
Velázquez-Campoy, Adrián
de Juan Romero, Camino
Neira, José L.
author_role author
author2 Fuentes-Baile, María
Rizzuti, Bruno
Bazan, J. Fernando
Villamarin-Ortiz, Adrián
Saceda, Miguel
Fernández, Eduardo
Vidal, Miguel
Abian, Olga
Velázquez-Campoy, Adrián
de Juan Romero, Camino
Neira, José L.
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Instituto de Salud Carlos III
Diputación General de Aragón
Generalitat Valenciana
Araujo-Abad, Salomé [0000-0001-7387-0363]
Fuentes-Baile, María [0000-0003-3653-2407]
Rizzuti, Bruno [0000-0003-1110-764X]
Bazan, J. Fernando [0000-0002-3645-9935]
Villamarin-Ortiz, Adrián [0000-0003-2768-9162]
Saceda, Miguel [0000-0002-1564-3602]
Vidal, Miguel [0000-0003-4374-6761]
Abian, Olga [0000-0001-5664-1729]
Velázquez-Campoy, Adrián [0000-0001-5702-4538]
de Juan Romero, Camino [0000-0001-7890-8447]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Intrinsically disordered proteins
Protein-protein interactions
Fluorescence
Proximity ligation assay
Isothermal titration calorimetry
Citrullination
topic Intrinsically disordered proteins
Protein-protein interactions
Fluorescence
Proximity ligation assay
Isothermal titration calorimetry
Citrullination
description 14 p.-6 fig.-1 tab.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023
2023
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/10261/336040
url http://hdl.handle.net/10261/336040
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.1016/j.ijbiomac.2023.125632
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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
_version_ 1869404763847655424
score 15,81155

Similares en LA Referencia