Margalef 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, Lluís2015-07-242015-07-242012Margalef P, Fernández-Majada V, Villanueva A, Garcia-Carbonell R, Iglesias M, López L et al. A truncated form of IKKα is responsible for specific nuclear IKK activity in colorectal cancer. Cell Rep. 2012 Oct 25;2(4):840-54. DOI: 10.1016/j.celrep.2012.08.0282211-1247http://hdl.handle.net/10230/24642Nuclear 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.application/pdfeng© 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-licenseTumorsCòlon -- Càncerinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.celrep.2012.08.028info:eu-repo/semantics/openAccess