Dubois, "Hypoxia-enhanced expression of the proprotein convertase furin is mediated by hypoxia-inducible factor-1: impact on the bioactivation of proproteins," The Journal of Biological Chemistry, vol.
Beside the active MMP-2 and MMP9 in ischemic neuronal nuclei at 3 h reperfusion, increased MT1-MMP and hypoxia-enhanced expression of the proprotein convertase furin were also detected in neuronal nuclei .
Cleavage by SPCs activates a variety of proproteins
, including hormones, growth factors, clotting factors, matrix-degrading metalloproteinases, receptors, and adhesion molecules.
Such multibasic motifs typically mark the cleavage sites of proproteins
from the mature molecule during the secretory process through the action of proprotein
convertases (Steiner, 1998; Seidah and Chretien, 1999).
A variety of proproteins
have been shown to be the substrates of furin (12, 13); however, the concept of furin involved in the processing of human proBNP is currently based on a set of indirect observations (14, 15).
Endoproteases of the Subtilisin-like Proprotein
Convertase (SPC) family cleave substrate proproteins
on the carboxy terminal side of a conserved sequence described as N-Arginine-X-X-Arginine-C.
convertases (SPCs) arc capable of processing a number of proproteins
in the secretory pathway known to affect nervous system development and synaptogenesis.
While all substrates contain this sequence, each widely expressed SPC has unique substrate preferences and many proproteins
are processed differentially by these enzymes.
These enzymes activate a diverse array of proproteins
that transit the secretary pathway.
While closely related to furin, the most well characterized member of this family, PACE4 has a restricted substrate range compared to furin, as PACE4 can process some, but not all, of the proproteins
furin can process.
A common biochemical feature of these candidates is that theyall derive from, or consist of, the proprotein
encoded by the corresponding gene.
Partial Purification and Characterization of Secreted Proprotein
Convertase Furin and PACE4.