A number of proteins have been identified as substrates for endoplasmic ret
iculum (ER)-associated protein degradation (ERAD) and we describe here a ne
w model substrate with which to study this process. Two secretion-defective
forms of yeast invertase that accumulated in the ER to greatly different l
evels were examined: Suc2-538p levels were low, while Suc2-533p was present
in high amounts. Because Suc2-533p and Suc2-538p mRNA levels were comparab
le, we examined whether Suc2-538p was targeted for degradation. Both mutant
polypeptide levels were unaffected in a yeast strain deficient in vacuolar
protease activity and, additionally, we showed that Suc2-538p was stabiliz
ed in ERAD-deficient strains, demonstrating that Suc2-538p was a substrate
for ERAD. Copyright (C) 2000 John Wiley & Sons, Ltd.