Identification of proteases with shared functions to the proprotein processing protease Krp1 in the fission yeast Schizosaccharomyces pombe

Many secretory proteins are synthesized as inactive proproteins that underg o proteolytic activation as they travel through the eukaryotic secretory pa thway. The best characterized family of processing enzymes are the prohormo ne convertases or kexins, and these are responsible for the processing of a wide variety of prohormones and other precursors. Recent work has identifi ed other proteases that appear to be involved in proprotein processing, but characterization of these enzymes is at an early stage. Krp1 is the only k exin identified in the fission yeast Schizosaccharomyces pombe, in which it is essential for cell viability. We have used a genetic screen to identify four proteases with specificities that overlap Krp1, Two are serine protea ses, one is a zinc metalloprotease (glycoproteaae) and one is an aspartyl p rotease that belongs to the recently described yapsin family of processing enzymes. All four proteases support the growth of a yeast strain lacking Kr p1, and each is able to process the P-factor precursor, the only substrate currently known to be processed by Krp1.