title: 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.
authors.affiliation: Vertex Pharmaceuticals Incorporated, Cambridge, MA 02139, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Gu
authors.forename: J
authors.initials: J
authors.lastname: Wu
authors.forename: C
authors.initials: C
authors.lastname: Faucheu
authors.forename: J L
authors.initials: JL
authors.lastname: Lalanne
authors.forename: A
authors.initials: A
authors.lastname: Diu
authors.forename: D J
authors.initials: DJ
authors.lastname: Livingston
authors.forename: M S
authors.initials: MS
authors.lastname: Su
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D020170:Caspase 1; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D005816:Genetic Complementation Test; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D014162:Transfection
chemical_list: D018076:DNA, Complementary; D003546:Cysteine Endopeptidases; D020170:Caspase 1