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Sci. STKE, 8 March 2005
Vol. 2005, Issue 274, p. tw86
[DOI: 10.1126/stke.2742005tw86]

EDITORS' CHOICE

IMMUNOLOGY Linking Caspase-8 and NF-{kappa}B Activation

The protease caspase-8 functions in signaling from death-inducing receptors on the cell surface, but analysis of humans lacking the enzyme suggests that it must also play a role in signaling from antigen and Fc receptors on cells in the immune system. Su et al. show that activation of nuclear factor {kappa}B (NF-{kappa}B, a key player in immune responses) is defective in cells lacking caspase-8. Antigen or Fc receptors stimulate NF-{kappa}B through a process mediated by a molecular complex that contains numerous signaling proteins, and caspase-8 physically interacts with adaptor proteins that aid in the formation of these signaling clusters. When it signals cell death, caspase-8 undergoes autoproteolysis that generates a fragment with strong protease activity. After activation of antigen receptors, however, catalytic activity of caspase-8 was still required for signaling, but the enzyme remained intact, perhaps in a conformation with a more moderate proteolytic activity. These results help explain the range of physiological effects seen in patients after the loss of this single protein-degrading enzyme.

H. Su, N. Bidère, L. Zheng, A. Cubre, K. Sakai, J. Dale, L. Salmena, R. Hakem, S. Straus, M. Lenardo, Requirement for caspase-8 in NF-{kappa}B activation by antigen receptor. Science 307, 1465-1468 (2005). [Abstract] [Full Text]

Citation: Linking Caspase-8 and NF-{kappa}B Activation. Sci. STKE 2005, tw86 (2005).



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