THE YEAST SSS1 GENE IS ESSENTIAL FOR SECRETORY PROTEIN TRANSLOCATION AND ENCODES A CONSERVED PROTEIN OF THE ENDOPLASMIC-RETICULUM

The SEC61, SEC62 and SEC63 yeast gene products are membrane components of the apparatus that catalyses protein translocation into the endoplasmic reticulum (ER). In the hope of uncovering additional components of the translocation apparatus, we sought yeast genes whose overexpression would restore partial thermoresistance in a sec61 translocation-deficient mutant. The first extragenic Sec sixty-one suppressor, SSS1, is an essential single copy gene whose overexpression restores translocation in the sec61 mutant. Another extragenic suppressor was identified as TDH3, which encodes the major isozyme of the most abundant yeast protein, glyceraldehyde-3-phosphate dehydrogenase. TDH3 overexpression could exert an indirect effect by competitively inhibiting protein synthesis, thereby allowing the impaired translocation apparatus to cope with a reduced flow of newly synthesized secretory proteins. Depletion of the Sss1 protein rapidly results in accumulation of multiple secretory or membrane proteins devoid of post-translational modifications; the normally secreted alpha-factor accumulates on the cytosolic side of ER membranes. Thus, the SSS1 gene is required for continued translocation of secretory preproteins beyond their early association to ER membranes. Consistent with its essential role in protein translocation, the Sss1 protein localizes to the ER and homologues were detected in higher eukaryotes.