Cysteine 73 in bleomycin hydrolase is critical for amyloid precursor protein processing.
Human bleomycin hydrolase (hBH) is a neutral cysteine protease that may regulate the secretion of soluble amyloid precursor protein (APP) and amyloid beta (A(beta)), which is a major constituent of the Alzheimer's disease-associated amyloid plaques. We have now determined that APP interacts with hBH by using yeast two hybrid methods and in vitro binding studies revealed that APP interacted with a 68 amino acid region that includes the catalytic domain of hBH. Ectopic expression of hBH increased the secretion of A(beta) but not of a second secreted protein, apolipoprotein A-I. Expression of hBH in which the catalytic cysteine 73 was mutated to serine failed to increase A(beta) secretion. These results indicate a critical role for cysteine 73 of hBH in mediating APP processing.
Lefterov
I M
IM
Department of Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Koldamova
R P
RP
Lefterova
M I
MI
Schwartz
D R
DR
Lazo
J S
JS
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D001483:Base Sequence; D016466:CHO Cells; D006224:Cricetinae; D003545:Cysteine / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D051379:Mice; D016297:Mutagenesis, Site-Directed; D011499:Protein Processing, Post-Translational
D016564:Amyloid beta-Protein Precursor; D016632:Apolipoprotein A-I; D017931:DNA Primers; D003546:Cysteine Endopeptidases; C031262:bleomycin hydrolase; D003545:Cysteine