Regulation of NF-κB Activation in T Cells via Association of the Adapter Proteins ADAP and CARMA1

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Science  04 May 2007:
Vol. 316, Issue 5825, pp. 754-758
DOI: 10.1126/science.1137895

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The adapter protein ADAP regulates T lymphocyte adhesion and activation. We present evidence for a previously unrecognized function for ADAP in regulating T cell receptor (TCR)–mediated activation of the transcription factor NF-κB. Stimulation of ADAP-deficient mouse T cells with antibodies to CD3 and CD28 resulted in impaired nuclear translocation of NF-κB, a reduced DNA binding, and delayed degradation and decreased phosphorylation of IκB (inhibitor of NF-κB). TCR-stimulated assembly of the CARMA1–BCL-10–MALT1 complex was substantially impaired in the absence of ADAP. We further identified a region of ADAP that is required for association with the CARMA1 adapter and NF-κB activation but is not required for ADAP-dependent regulation of adhesion. These findings provide new insights into ADAP function and the mechanism by which CARMA1 regulates NF-κB activation in T cells.

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