The metabolic pathways governing the turnover of presenilin 1 (PS I) h
ave been incompletely worked out. The PS 1 holoprotein has low abundan
ce in many cells and appears to undergo endoproteolytic cleavage near
residue 298. We provide evidence that one mechanism by which the PSI h
oloprotein is degraded is through the action of the 26S proteasome. We
also show that the proteasome does not participate in the endoproteol
ytic cleavage. (C) 1998 Elsevier Science Inc.