Biosynthetic processing and quaternary interactions of proprotein convertase SPC4 (PACE4)

FEBS Letters

Taniguchi, Takazumi¹  Mori, Kenji¹  Matsuda, Yoshiko¹  Nagahama, Masami¹  Tsuji, Akihiko¹  Hashimoto, Emi¹  Imamaki, Akiyoshi¹ 

[1] Department of Biological Science and Technology, Faculty of Engineering, The University of Tokushima, 2-1 Minamijosanjima, Tokushima 770-8506, Japan

关键词: SPC4;    PACE4;    Processing protease;    Endoplasmic reticulum;    Proenzyme activation;    Oligomerization;   

DOI  :  10.1016/S0014-5793(98)00970-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown