Casein kinase 1α governs antigen-receptor-induced NF-κB activation and human lymphoma cell survival

Nicolas Bidère, Vu N. Ngo, Jeansun Lee, Cailin Collins, Lixin Zheng, Fengyi Wan, R. Eric Davis, Georg Lenz, D. Eric Anderson, Damien Arnoult, Aimé Vazquez, Keiko Sakai, Jun Zhang, Zhaojing Meng, Timothy D. Veenstra, Louis M. Staudt () and Michael J. Lenardo ()
Additional contact information
Nicolas Bidère: Molecular Development Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases
Vu N. Ngo: Metabolism Branch, Center for Cancer Research, National Cancer Institute,
Jeansun Lee: Molecular Development Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases
Cailin Collins: Metabolism Branch, Center for Cancer Research, National Cancer Institute,
Lixin Zheng: Molecular Development Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases
Fengyi Wan: Molecular Development Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases
R. Eric Davis: Metabolism Branch, Center for Cancer Research, National Cancer Institute,
Georg Lenz: Metabolism Branch, Center for Cancer Research, National Cancer Institute,
D. Eric Anderson: Proteomics and Mass Spectrometry Facility, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
Damien Arnoult: U542, INSERM, Université Paris-Sud, Hôpital Paul Brousse, Villejuif 94800, France
Aimé Vazquez: U542, INSERM, Université Paris-Sud, Hôpital Paul Brousse, Villejuif 94800, France
Keiko Sakai: Molecular Development Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases
Jun Zhang: Molecular Development Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases
Zhaojing Meng: Laboratory of Proteomics and Analytical Technologies (LPAT), National Cancer Institute, Frederick, Maryland 21702, USA
Timothy D. Veenstra: Laboratory of Proteomics and Analytical Technologies (LPAT), National Cancer Institute, Frederick, Maryland 21702, USA
Louis M. Staudt: Metabolism Branch, Center for Cancer Research, National Cancer Institute,
Michael J. Lenardo: Molecular Development Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases

Nature, 2009, vol. 458, issue 7234, 92-96

Abstract: Lymphocyte activation The CBM protein complex, consisting of the scaffold protein CARMA1, the adaptor protein BCL10 and the paracaspase enzyme MALT1, has a key role in transducing signals from the antigen receptors in T and B cells to the transcription factor NF-κB during lymphocyte activation. How this important protein complex is regulated has remained obscure but now Bidère et al. show that the CBM complex is regulated in two opposing ways by casein kinase 1α (CK1α), first promoting and then terminating receptor-induced NF-κB activity and lymphocyte activation. CK1α is also required for the constitutive NF-κB signalling found in lymphoma cells. This dual 'gating' function suggests that CK1α can act as a conditionally essential malignancy gene— potentially representing a new class of cancer therapeutic targets.

Date: 2009
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DOI: 10.1038/nature07613

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