Caspase-1

Literature References: Primary protease responsible for cleavage of the proinflammatory cytokines interleukin-1b (IL-1b) and interleukin-18 (IL-18) from their biologically inactive precursors. IL-1b is the predominant form of interleukin-1, q.v., produced by human monocytes. Caspase-1 is synthesized as an inactive 45 kDa precursor protein, procaspase-1, that is cleaved to form an active heterodimer composed of 10 and 20 kDa subunits. Identification in monocytes and IL-1b activation: M. J. Kostura et al., Proc. Natl. Acad. Sci. USA 86, 5227 (1989); R. A. Black et al., FEBS Lett. 247, 386 (1989). Purification, primary structure and catalytic mechanism: N. A. Thornberry et al., Nature 356, 768 (1992). Molecular cloning of human cDNA: D. P. Cerretti et al., Science 256, 97 (1992). Induction of apoptosis in fibroblasts: M. Miura et al., Cell 75, 653 (1993). Crystal structure of recombinant human form: N. P. C. Walker et al., ibid. 78, 343 (1994); and mechanism of action: K. P. Wilson et al., Nature 370, 270 (1994). Activation of IL-18 (interferon-g-inducing factor): T. Ghayur et al., ibid. 386, 619 (1997). Overexpression in chronic pancreatitis: M. Ramadani et al., Pancreas 22, 383 (2001); in multiple sclerosis plaques: X. Ming et al., J. Neurol. Sci. 197, 9 (2002). Review of assay methods, purification and inhibition: N. A. Thornberry, Methods Enzymol. 244, 615-631 (1994); of structure and function: M. J. Tocci, Vitam. Horm. 53, 27-63 (1997), of role in intestinal inflammation: B. Siegmund, Biochem. Pharmacol. 64, 1-8 (2002).