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Science 4 March 2005:
Vol. 307. no. 5714, p. 1371
DOI: 10.1126/science.307.5714.1371j
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This Week in Science

Figure 3 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. (p. 1465) show that activation of nuclear factor B (NF-B, a key player in immune responses) is defective in cells lacking caspase-8. Antigen or Fc receptors stimulate NF-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 loss of this single protein-degrading enzyme.

CREDIT: SU ET AL.




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Science. ISSN 0036-8075 (print), 1095-9203 (online)