title: Biosynthetic processing and quaternary interactions of proprotein convertase SPC4 (PACE4).
abstract: SPC4 (PACE4), a member of the eukaryotic family of subtilisin-like proprotein convertases, is synthesized as a proenzyme (proSPC4) which undergoes proteolytic removal of N-terminal propeptide during transit through the secretory pathway. As this propeptide processing seems to be a key event in the functional expression of SPC4, we have investigated its mechanism and the intracellular site where it occurs. In transfected fibroblast cells, the 110-kDa proSPC4 undergoes slow cleavage to generate a 103-kDa mature enzyme in the endoplasmic reticulum (ER). Site-directed mutagenesis studies demonstrate that the proteolytic activation of SPC4 occurs mainly through a unimolecular autocatalytic process and propeptide cleavage is a prerequisite for its export from the ER. Sedimentation velocity and chemical cross-linking analysis demonstrate that the precursor protein in the cells exists as both a monomer and a dimer-sized complex whereas mature SPC4 exists only as a monomer. These results suggest that the cleavage of the N-terminal propeptide of SPC4 plays a regulatory role in its activation and secretion through the change in its oligomeric state.
authors.affiliation: Department of Biological Science and Technology, Faculty of Engineering, The University of Tokushima, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nagahama
authors.forename: T
authors.initials: T
authors.lastname: Taniguchi
authors.forename: E
authors.initials: E
authors.lastname: Hashimoto
authors.forename: A
authors.initials: A
authors.lastname: Imamaki
authors.forename: K
authors.initials: K
authors.lastname: Mori
authors.forename: A
authors.initials: A
authors.lastname: Tsuji
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D002460:Cell Line; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis* / Q000737:chemistry; D043484:Proprotein Convertases; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000737:chemistry
chemical_list: D007527:Isoenzymes; C080654:PCSK6 protein, human; D043484:Proprotein Convertases; D012697:Serine Endopeptidases