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Title: A Truncated Form of IKKa Is Responsible for Specific Nuclear IKK Activity in Colorectal Cancer
Author: Margalef, Pol
Fernández Majada, Vanessa
Villanueva Garatachea, Alberto
Garcia Carbonell, Ricard
Iglesias, Mar
López, Laura
Martínez Iniesta, María
Villà Freixa, Jordi
Mulero Roig, María Carmen
Andreu, Montserrat
Torres, Ferran
Mayo, Marty W.
Bigas Salvans, Anna
Espinosa, Lluis
Keywords: Càncer colorectal
Colorectal cancer
Issue Date: 4-Oct-2012
Publisher: Cell Press
Abstract: Nuclear IKK alpha regulates gene transcription by phosphorylating specific substrates and has been linked to cancer progression and metastasis. However, the mechanistic connection between tumorigenesis and IKK alpha 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 IKK alpha isoform with a predicted molecular weight of 45 kDa (p45-IKK alpha) that includes the kinase domain but lacks several regulatory regions. Active nuclear p45-IKK alpha forms a complex with nonactive IKK alpha and NEMO that mediates phosphorylation of SMRT and histone H3. Proteolytic cleavage of FL-IKK alpha into p45-IKK alpha 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.
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It is part of: Cell Reports, 2012, vol. 2, num. 4, p. 840-854
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Appears in Collections:Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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