Proteolytic processing and degradation of human presenilin-1 expressed in yeast.
Numerous mutations causing early-onset familial Alzheimer's disease have been identified in the presenilin-1 gene. Presenilin-1 protein is produced as a 47 kDa holoprotein and proteolytically processed to an N-terminal 28 kDa and a C-terminal 19 kDa fragments by unidentified presenilinase in mammalian cells. We have demonstrated that this proteolytic processing also occurs in yeast. We also show that degradation of C-terminal fragment of presenilin-1 is dependent of proteasomal function. This yeast system will be a good tool to identify presenilinase and to study the role of presenilin-1 in amyloid precursor protein processing.
Song
S
S
Mitsubishi Kasei Institute of Life Sciences, 11 Minamiooya, Machida-shi, Tokyo, Japan.
Ohba
M
M
Saito
Y
Y
Honda
T
T
Takashima
A
A
Takahashi
H
H
D015153:Blotting, Western; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism; D009154:Mutation; D053764:Presenilin-1; D046988:Proteasome Endopeptidase Complex; D012441:Saccharomyces cerevisiae / Q000378:metabolism*
D008565:Membrane Proteins; D009097:Multienzyme Complexes; C508853:PSEN1 protein, human; D053764:Presenilin-1; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex