Determining the Destiny of NF-κ B after TCR Ligation: It’s CARMA1

  1. Stephen C. Bunnell
  1. Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA

Abstract

In T lymphocytes, the “novel” protein kinase C ?? (PKC ??) isoform and the transcription factor nuclear factor-κB (NF-κB) are required for cell proliferation and the production of cytokines in response to T cell activation; however, the molecular interactions that link PKC?? and NF-κB have remained unknown. Two recent reports demonstrate that CARMA1 (caspase recruitment domain-containing membrane-associated guanylate kinase protein-1) bridges the gap between PKC?? and the IκB kinase (IKK)-dependent activation of NF-κB in T cells. Excessive T lymphocyte activation and proliferation are hallmarks of T cell-derived leukemias. Given that CARMA1 is specifically expressed in lymphoid tissues, could pharmacological inhibitors be designed to inhibit CARMA1’s (or PKC??’s) ability to promote the activation of NF-κB?

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