Functional characterization of the prodomain of interleukin-1beta-converting enzyme.
Interleukin-1beta-converting enzyme (ICE) has been identified as the main protease responsible for maturation of the prodomain of interleukin-1beta. Recently, it was shown to belong to a larger gene family, members of which play an important role in programmed cell death. A common feature of the ICE family proteases is the presence of a prodomain that has been hypothesized to keep the enzyme in an inactive form. Expression analysis in yeast revealed autocatalytic degradation of p45ICE, but not of p30ICE lacking a prodomain. We further demonstrate that p45ICE, in which the critical cysteine has been mutated, is still able to dimerize in vivo. Dimerization requires the prodomain and occurs prior to autoprocessing. These results provide evidence for a regulatory role of the prodomain of ICE.
Laboratory of Molecular Biology, Flanders Interuniversity Institute for Biotechnology and University of Ghent, B-9000 Ghent, Belgium.
W
W
Van Criekinge
R
R
Beyaert
M
M
Van de Craen
P
P
Vandenabeele
P
P
Schotte
D
D
De Valck
W
W
Fiers
D000818:Animals; D020170:Caspase 1; D003001:Cloning, Molecular; D003546:Cysteine Endopeptidases / Q000096:biosynthesis / Q000378:metabolism*; D019281:Dimerization; D004792:Enzyme Precursors / Q000378:metabolism*; D015723:Gene Library; D017930:Genes, Reporter; D007700:Kinetics; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D001616:beta-Galactosidase / Q000096:biosynthesis
D004792:Enzyme Precursors; D011993:Recombinant Fusion Proteins; D001616:beta-Galactosidase; D003546:Cysteine Endopeptidases; D020170:Caspase 1