Activation and nuclear translocation of the immune-response transcription factor nuclear factor-κB (NF-κB) depends on signals that emanate from a variety of cell-surface receptors. Two membrane-proximal caspase-recruitment proteins, CARMA1 and Bcl10, form part of the chain of signaling events, but other critical remaining steps in the pathway have yet to be established. Ruefli-Brasse et al. (see the Perspective by Yu and Lenardo) show that the caspase-like protein, paracaspase, is essential for lymphocyte function and acts downstream of CARMA1 and Bcl10. Impaired paracaspase-dependent activation of the kinase complex that normally facilitates NF-κB activation caused T and B cells from paracaspase-deficient mice to respond poorly to receptor signals.
A. A. Ruefli-Brasse, D. M. French, V. M. Dixit, Regulation of NF-κB-dependent lymphocyte activation and development by paracaspase. Science 302, 1581-1584 (2003). [Abstract] [Full Text]
L. Yu, M. J. Lenardo, Paracaspase connection. Science 302, 1515-1516 (2003). [Abstract] [Full Text]
