A NEW LARGE PROTEOLYTIC COMPLEX DISTINCT FROM THE PROTEASOME IS PRESENT IN THE CYTOSOL OF FISSION YEAST

One eukaryotic proteolytic complex - the proteasome - is classed as th e major nonlysosomal protease, by its known and suspected functions, i ts size and its complexity [1,2], It seems improbable that other enzym es may be capable of substituting, even partially, for the potent prot easome, as this complex has a vital role in many cellular processes [1 -3], Nevertheless, it is possible to adapt cultured EL-4 mouse lymphom a cells to survive in the presence of a specific inhibitor of the prot easome [4], The inhibition of the proteasome in these adapted EL-4 cel ls is accompanied by a dramatic increase in the activity of a new, as yet uncharacterized, large proteolytic complex [4]. Here, we have pres ented evidence that a similar proteolytic activity is constitutively p resent in fission yeast, Schizosaccharomyces pombe, and that the yeast and mouse enzymes share basic physicochemical properties. We have sho wn that the S. pombe protease is found in two stable oligomeric forms, both of which are peptidases, although only the larger form acts as a proteinase. The relative amounts of the large and the small forms of the protease in the complex depended on the growth phase of the yeast culture and affected enzyme activity, suggesting that the activity of the enzyme is regulated by its oligomerization status. We refer to the new proteolytic complex as the 'multicorn' to indicate its analogy to the archaebacterial tricorn protease [5].