THE HOMOLOG OF MAMMALIAN SPC12 IS IMPORTANT FOR EFFICIENT SIGNAL PEPTIDASE ACTIVITY IN SACCHAROMYCES-CEREVISIAE

The multisubunit signal peptidase catalyzes the cleavage of signal pep tides and the degradation of some membrane proteins within the endopla smic reticulum (ER). The only subunit of this enzyme functionally exam ined to date, yeast Sec11p, is related to signal peptidase I from bact eria. Since bacterial signal peptidase is capable of processing both p rokaryotic and eukaryotic signal sequences as a monomer, it is unclear why the analogous enzyme in the ER contains proteins unrelated to sig nal peptidase I. To address this issue, the gene encoding Spc1p, the y east homologue to mammalian SPC12, is isolated from the yeast Saccharo myces cerevisiae, Spc1p co-purifies and genetically interacts with Sec 11p, but unlike Sec11p, Spc1p is not required for cell growth or the p roteolytic processing of tested proteins in yeast, This indicates that only a subset of the ER signal peptidase subunits is required for sig nal peptidase and protein degradation activities in vivo. Through both genetic and biochemical criteria. Spc1p appears, however, to be impor tant for efficient signal peptidase activity.