Interleukin-1 beta converting enzyme requires oligomerization for activity of processed forms in vivo.

Abstract

Interleukin‐1 beta converting enzyme (ICE) is composed of 10′ (p10) and 20 kDa (p20) subunits, which are derived from a common 45 kDa precursor. Recent crystallographic studies have shown that ICE exists as a tetramer (p20/p10)2 in the crystal lattice. We provide evidence that the p10 and p20 subunits of ICE associate as oligomers in transfected COS cells. Using intragenic complementation, we show that the activity of a p10/p10 interface mutant defective in autoprocessing can be restored by co‐expression with active site ICE mutants. Different active site mutants can also complement each other by oligomerization to form active ICE. These studies indicate that ICE precursor polypeptides may associate in different quaternary structures and that oligomerization is required for autoprocessing. Furthermore, integenic complementation of active site mutants of ICE and an ICE homolog restores autoprocessing activity, suggesting that hetero‐oligomerization occurs between ICE homologs.

Origin, expression and possible functions of the two alternatively spliced forms of the mouse Nedd2 mRNA

“…Cross species interactions between subunits derived from different ICE-like proteases has been demonstrated (eg. Gu et al, 1995;Fernandes-Alnemri et al, 1995). Whether Nedd2s also functions to inhibit apoptosis in Rat-1 and NIH-3T3 cells by interacting with the smaller subunits of other caspases, remains to be determined.…”

Caspases: the executioners of apoptosis

“…The alternative, but less favoured, model suggested processing followed by association of the subunits [41]. Using various active-site mutants, it has been shown that oligomerization of caspase-1 is required for autoprocessing [42] and that hetero-oligomerization may occur between different caspase homologues, but the in i o relevance of this is not known. Using the yeast two-hybrid system, the prodomain of caspase-1 is absolutely required for dimerization and autoproteolysis, suggesting a regulatory rather than a structural role for the prodomain [43].…”

Serial killers: ordering caspase activation events in apoptosis

“…18 Comparatively little is known about the caspases that are involved in cytokine processing and the manner in which they are activated beyond the fact that caspase-11-deficient mice are unable to activate caspase-1 and that caspase-1 may be activated by oligomerization. 19,20 However, our knowledge of the manner in which activation of the cell death-related caspases is achieved is more advanced and will form the basis for much of the subsequent discussion.…”