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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7234
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pubmed:dateCreated |
2009-3-5
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pubmed:abstractText |
The transcription factor NF-kappaB is required for lymphocyte activation and proliferation as well as the survival of certain lymphoma types. Antigen receptor stimulation assembles an NF-kappaB activating platform containing the scaffold protein CARMA1 (also called CARD11), the adaptor BCL10 and the paracaspase MALT1 (the CBM complex), linked to the inhibitor of NF-kappaB kinase complex, but signal transduction is not fully understood. We conducted parallel screens involving a mass spectrometry analysis of CARMA1 binding partners and an RNA interference screen for growth inhibition of the CBM-dependent 'activated B-cell-like' (ABC) subtype of diffuse large B-cell lymphoma (DLBCL). Here we report that both screens identified casein kinase 1alpha (CK1alpha) as a bifunctional regulator of NF-kappaB. CK1alpha dynamically associates with the CBM complex on T-cell-receptor (TCR) engagement to participate in cytokine production and lymphocyte proliferation. However, CK1alpha kinase activity has a contrasting role by subsequently promoting the phosphorylation and inactivation of CARMA1. CK1alpha has thus a dual 'gating' function which first promotes and then terminates receptor-induced NF-kappaB. ABC DLBCL cells required CK1alpha for constitutive NF-kappaB activity, indicating that CK1alpha functions as a conditionally essential malignancy gene-a member of a new class of potential cancer therapeutic targets.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-10517632,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-10676951,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-11163238,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-11748286,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-11955436,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-12075054,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-12154356,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-12154360,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-12818158,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-12867037,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-12867038,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-14576442,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-14586424,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-14614861,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-15746428,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-16301747,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-16341016,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-16356855,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-16356856,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-16481469,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-16572121,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-16818229,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-16920630,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-17098202,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-17363905,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-17889643,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-17948050,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-18045535,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-18323416,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19118383-18568025
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/BCL10 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CARD Signaling Adaptor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/CARD11 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Casein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Guanylate Cyclase,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/MALT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1476-4687
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pubmed:author |
pubmed-author:AndersonD EricDE,
pubmed-author:ArnoultDamienD,
pubmed-author:BidèreNicolasN,
pubmed-author:CollinsCailinC,
pubmed-author:DavisR EricRE,
pubmed-author:LeeJeansunJ,
pubmed-author:LenardoMichael JMJ,
pubmed-author:LenzGeorgG,
pubmed-author:MengZhaojingZ,
pubmed-author:NgoVu NVN,
pubmed-author:SakaiKeikoK,
pubmed-author:StaudtLouis MLM,
pubmed-author:VazquezAiméA,
pubmed-author:VeenstraTimothy DTD,
pubmed-author:WanFengyiF,
pubmed-author:ZhangJunJ,
pubmed-author:ZhengLixinL
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pubmed:issnType |
Electronic
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pubmed:day |
5
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pubmed:volume |
458
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
92-6
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:19118383-Humans,
pubmed-meshheading:19118383-Lymphoma, Large B-Cell, Diffuse,
pubmed-meshheading:19118383-Cells, Cultured,
pubmed-meshheading:19118383-Neoplasm Proteins,
pubmed-meshheading:19118383-Protein Binding,
pubmed-meshheading:19118383-Cell Survival,
pubmed-meshheading:19118383-Cell Proliferation,
pubmed-meshheading:19118383-Signal Transduction,
pubmed-meshheading:19118383-Guanylate Cyclase,
pubmed-meshheading:19118383-Feedback, Physiological,
pubmed-meshheading:19118383-Receptors, Antigen,
pubmed-meshheading:19118383-Casein Kinases,
pubmed-meshheading:19118383-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:19118383-NF-kappa B,
pubmed-meshheading:19118383-Caspases,
pubmed-meshheading:19118383-Jurkat Cells,
pubmed-meshheading:19118383-I-kappa B Kinase,
pubmed-meshheading:19118383-CARD Signaling Adaptor Proteins
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