HtrA2 interacts with A beta peptide but does not directly alter its production or degradation.
HtrA2/Omi is a mammalian mitochondrial serine protease homologous to the E. coli HtrA/DegP gene products. Recently, HtrA2/Omi was found to have a dual role in mammalian cells, acting as an apoptosis-inducing protein and being involved in maintenance of mitochondrial homeostasis. By screening a human brain cDNA library with A beta peptide as bait in a yeast two-hybrid system, we identified HtrA2/Omi as a binding partner of A beta peptide. The interaction between A beta peptide and HtrA2/Omi was confirmed by an immunoblot binding assay. The possible involvement of HtrA2/Omi in A beta peptide metabolism was investigated. In vitro peptide cleavage assays showed that HtrA2/Omi did not directly promote the production of A beta peptide at the beta/gamma-secretase level, or the degradation of A beta peptide. However, overexpression of HtrA2/Omi in K269 cells decreased the production of A beta40 and A beta42 by up to 30%. These results rule out the involvement of HtrA2/Omi in the etiology of Alzheimer's disease. However, the fact that overexpression of HtrA2/Omi reduces the generation of A beta40 and A beta42 suggests that it may play some positive role in mammalian cells.
Liu
Meng-Lu
ML
Department of Microbiology and Research Center for Industrial Development of Biofood Materials, Chonbuk National University Medical School, Jeonju 561-756, Korea.
Liu
Ming-Jie
MJ
Kim
Jin-Man
JM
Kim
Hyeon-Jin
HJ
Kim
Jeong-Hak
JH
Hong
Seong-Tshool
ST
D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D016282:Aspartic Acid Endopeptidases; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D010450:Endopeptidases / Q000378:metabolism; D015723:Gene Library; D000074923:High-Temperature Requirement A Serine Peptidase 2; D006801:Humans; D024101:Mitochondrial Proteins; D012697:Serine Endopeptidases / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014162:Transfection; D020798:Two-Hybrid System Techniques
D016229:Amyloid beta-Peptides; D024101:Mitochondrial Proteins; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D012697:Serine Endopeptidases; C000615914:HTRA2 protein, human; D000074923:High-Temperature Requirement A Serine Peptidase 2; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human