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

FEBS Letters - Tập 434 - Trang 155-159 - 1998
Masami Nagahama1, Takazumi Taniguchi1, Emi Hashimoto1, Akiyoshi Imamaki1, Kenji Mori1, Akihiko Tsuji1, Yoshiko Matsuda1
1Department of Biological Science and Technology, Faculty of Engineering, The University of Tokushima, 2-1 Minamijosanjima, Tokushima 770-8506, Japan

Tóm tắt

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.

Tài liệu tham khảo

10.1016/0300-9084(94)90147-3 10.1006/frne.1995.1012 10.1042/bj3270625 10.1089/dna.1991.10.757 10.1006/bbrc.1994.1541 10.1016/0014-5793(96)01059-9 10.1093/oxfordjournals.jbchem.a021677 10.1006/bbrc.1994.2060 10.1210/en.136.1.357 10.1007/s004180050150 10.1083/jcb.134.1.181 Hubbard F.C., 1997, Cancer Res., 57, 5226 10.1093/oxfordjournals.jbchem.a021772 10.1042/bj3210587 10.1016/0014-5793(93)80589-M 10.1016/S0021-9258(18)67398-3 10.1083/jcb.109.1.61 10.1042/bj2990001 10.1016/S0021-9258(19)49712-3 10.1016/S0021-9258(20)80616-4 10.1006/bbrc.1994.1771 10.1002/j.1460-2075.1994.tb06231.x 10.1016/S0021-9258(17)32459-6 10.1074/jbc.272.43.27116 10.1093/emboj/16.7.1508 10.1210/me.6.7.1088 10.1016/S0021-9258(17)32323-2 10.1074/jbc.270.42.24702 10.1074/jbc.272.24.15184 10.1016/0014-5793(91)80703-6 10.1016/0092-8674(94)90296-8 10.1016/S0021-9258(17)42389-1 10.1074/jbc.270.3.1402 10.1083/jcb.129.6.1641
Thông tin
Thông tin xuất bản

FEBS Letters

Tập 434

155-159

Thông tin tác giả