A truncated form of IKKα is responsible for specific nuclear IKK activity in colorectal cancer

Margalef González, Pol, 1985-; Fernández Majada, Vanessa; Villanueva, Alberto; Garcia Carbonell, Ricard; Iglesias Coma, Mar; López Muñoz, Laura; Martínez Iniesta, María; Villà i Freixa, Jordi; Mulero, María Carmen; Andreu García, Montserrat; Torres, Ferran; Mayo, Marty W.; Bigas Salvans, Anna; Espinosa Blay, Lluís

A truncated form of IKKα is responsible for specific nuclear IKK activity in colorectal cancer

Nuclear IKKα regulates gene transcription by phosphorylating specific substrates and has been linked to cancer progression and metastasis. However, the mechanistic connection between tumorigenesis and IKKα activity remains poorly understood. We have now analyzed 288 human colorectal cancer samples a...

Descripción completa

Detalles Bibliográficos
Autores:	Margalef González, Pol, 1985-, Fernández Majada, Vanessa, Villanueva, Alberto, Garcia Carbonell, Ricard, Iglesias Coma, Mar, López Muñoz, Laura, Martínez Iniesta, María, Villà i Freixa, Jordi, Mulero, María Carmen, Andreu García, Montserrat, Torres, Ferran, Mayo, Marty W., Bigas Salvans, Anna, Espinosa Blay, Lluís
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2012
País:	España
Institución:	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:10230/24642
Acceso en línea:	http://hdl.handle.net/10230/24642 http://dx.doi.org/10.1016/j.celrep.2012.08.028
Access Level:	acceso abierto
Palabra clave:	Tumors Còlon -- Càncer

id	ES_a41f4a75ad00f9478564e0361680ade9
oai_identifier_str	oai:recercat.cat:10230/24642
network_acronym_str	ES
network_name_str	España
repository_id_str
spelling	A truncated form of IKKα is responsible for specific nuclear IKK activity in colorectal cancerMargalef González, Pol, 1985-Fernández Majada, VanessaVillanueva, AlbertoGarcia Carbonell, RicardIglesias Coma, MarLópez Muñoz, LauraMartínez Iniesta, MaríaVillà i Freixa, JordiMulero, María CarmenAndreu García, MontserratTorres, FerranMayo, Marty W.Bigas Salvans, AnnaEspinosa Blay, LluísTumorsCòlon -- CàncerNuclear IKKα regulates gene transcription by phosphorylating specific substrates and has been linked to cancer progression and metastasis. However, the mechanistic connection between tumorigenesis and IKKα activity remains poorly understood. We have now analyzed 288 human colorectal cancer samples and found a significant association between the presence of nuclear IKK and malignancy. Importantly, the nucleus of tumor cells contains an active IKKα isoform with a predicted molecular weight of 45 kDa (p45-IKKα) that includes the kinase domain but lacks several regulatory regions. Active nuclear p45-IKKα forms a complex with nonactive IKKα and NEMO that mediates phosphorylation of SMRT and histone H3. Proteolytic cleavage of FL-IKKα into p45-IKKα is required for preventing the apoptosis of CRC cells in vitro and sustaining tumor growth in vivo. Our findings identify a potentially druggable target for treating patients with advance refractory CRC.P.M. is a recipient of a FPU fellowship (AP2009-2892) and M.C.M. is funded by the ‘‘Sara Borrell’’ Program from MICIN (CD09/00421). This work was supported by Fondo de Investigaciones Sanitarias (PI07/0778 and PI10/01128), AGAUR (2009SGR23), Fondos Feder RD06/0020/0098 and RD09/0076/00036, and Xarxa de Bancs de tumors sponsored by Pla Director d’Oncologia de/nCatalunya (XBTC). M.W.M. was supported by funds from the NIH/NCI R01 CA104397Elsevier201520152012info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/24642http://dx.doi.org/10.1016/j.celrep.2012.08.028reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésJournal of experimental medicine. 2012 Oct 25;2(4):840-54© Elsevier This is the published version of an article http://dx.doi.org/10.1016/j.celrep.2012.08.028 that appeared in the journal Cell reports. It is published in an Open Archive under an Elsevier user license. Details of this licence are available here: http://www.elsevier.com/about/open-access/open-access-policies/oa-license-policy/elsevier-user-licenseinfo:eu-repo/semantics/openAccessoai:recercat.cat:10230/246422026-05-29T05:05:01Z
dc.title.none.fl_str_mv	A truncated form of IKKα is responsible for specific nuclear IKK activity in colorectal cancer
title	A truncated form of IKKα is responsible for specific nuclear IKK activity in colorectal cancer
spellingShingle	A truncated form of IKKα is responsible for specific nuclear IKK activity in colorectal cancer Margalef González, Pol, 1985- Tumors Còlon -- Càncer
title_short	A truncated form of IKKα is responsible for specific nuclear IKK activity in colorectal cancer
title_full	A truncated form of IKKα is responsible for specific nuclear IKK activity in colorectal cancer
title_fullStr	A truncated form of IKKα is responsible for specific nuclear IKK activity in colorectal cancer
title_full_unstemmed	A truncated form of IKKα is responsible for specific nuclear IKK activity in colorectal cancer
title_sort	A truncated form of IKKα is responsible for specific nuclear IKK activity in colorectal cancer
dc.creator.none.fl_str_mv	Margalef González, Pol, 1985- Fernández Majada, Vanessa Villanueva, Alberto Garcia Carbonell, Ricard Iglesias Coma, Mar López Muñoz, Laura Martínez Iniesta, María Villà i Freixa, Jordi Mulero, María Carmen Andreu García, Montserrat Torres, Ferran Mayo, Marty W. Bigas Salvans, Anna Espinosa Blay, Lluís
author	Margalef González, Pol, 1985-
author_facet	Margalef González, Pol, 1985- Fernández Majada, Vanessa Villanueva, Alberto Garcia Carbonell, Ricard Iglesias Coma, Mar López Muñoz, Laura Martínez Iniesta, María Villà i Freixa, Jordi Mulero, María Carmen Andreu García, Montserrat Torres, Ferran Mayo, Marty W. Bigas Salvans, Anna Espinosa Blay, Lluís
author_role	author
author2	Fernández Majada, Vanessa Villanueva, Alberto Garcia Carbonell, Ricard Iglesias Coma, Mar López Muñoz, Laura Martínez Iniesta, María Villà i Freixa, Jordi Mulero, María Carmen Andreu García, Montserrat Torres, Ferran Mayo, Marty W. Bigas Salvans, Anna Espinosa Blay, Lluís
author2_role	author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Tumors Còlon -- Càncer
topic	Tumors Còlon -- Càncer
description	Nuclear IKKα regulates gene transcription by phosphorylating specific substrates and has been linked to cancer progression and metastasis. However, the mechanistic connection between tumorigenesis and IKKα activity remains poorly understood. We have now analyzed 288 human colorectal cancer samples and found a significant association between the presence of nuclear IKK and malignancy. Importantly, the nucleus of tumor cells contains an active IKKα isoform with a predicted molecular weight of 45 kDa (p45-IKKα) that includes the kinase domain but lacks several regulatory regions. Active nuclear p45-IKKα forms a complex with nonactive IKKα and NEMO that mediates phosphorylation of SMRT and histone H3. Proteolytic cleavage of FL-IKKα into p45-IKKα is required for preventing the apoptosis of CRC cells in vitro and sustaining tumor growth in vivo. Our findings identify a potentially druggable target for treating patients with advance refractory CRC.
publishDate	2012
dc.date.none.fl_str_mv	2012 2015 2015
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	http://hdl.handle.net/10230/24642 http://dx.doi.org/10.1016/j.celrep.2012.08.028
url	http://hdl.handle.net/10230/24642 http://dx.doi.org/10.1016/j.celrep.2012.08.028
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Journal of experimental medicine. 2012 Oct 25;2(4):840-54
dc.rights.none.fl_str_mv	info:eu-repo/semantics/openAccess
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf application/pdf
dc.publisher.none.fl_str_mv	Elsevier
publisher.none.fl_str_mv	Elsevier
dc.source.none.fl_str_mv	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_	1869415471537717248
score	15,81155

A truncated form of IKKα is responsible for specific nuclear IKK activity in colorectal cancer

Similares en LA Referencia