Cleavage of amyloid-β precursor protein (APP) by membrane-type matrix metalloproteinases
| Autor: | Munirah Ahmad, Takahisa Takino, Hiroshi Sato, Tomokazu Yoshizaki, Mitsuru Furukawa, Hisashi Miyamori |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Amyloid-β precursor protein
Peptide Biochemistry Cell Line Transactivation Amyloid beta-Protein Precursor mental disorders Chlorocebus aethiops Amyloid precursor protein Animals Humans Molecular Biology Cleavage chemistry.chemical_classification MT-MMP biology MMP Hydrolysis P3 peptide General Medicine Molecular biology Matrix Metalloproteinases Biochemistry of Alzheimer's disease Ectodomain chemistry Alpha secretase Expression cloning COS Cells biology.protein |
| Zdroj: | Journal of Biochemistry. 139(3):517-526 |
| ISSN: | 0021-924X |
| Popis: | 金沢大学がん研究所がん病態制御 Amyloid-β precursor protein (APP) was identified on expression cloning from a human placenta cDNA library as a gene product that modulates the activity of membrane-type matrix metalloproteinase-1 (MT1-MMP). Co-expression of MT1-MMP with APP in HEK293T cells induced cleavage and shedding of the APP ectodomain when co-expressed with APP adaptor protein Fe65. Among the MT-MMPs tested, MT3-MMP and MT5-MMP also caused efficient APP shedding. The recombinant APP protein was cleaved by MT3-MMP in vitro at the A463-M 464, N579-M580, H622-S 623, and H685-Q686 peptide bonds, which included a cleavage site within the amyloid β peptide region known to produce a C-terminal fragment. The Swedish-type mutant of APP, which produces a high level of amyloid β peptide, was more effectively cleaved by MT3-MMP than wild-type APP in both the presence and absence of Fe65; however, amyloid β peptide production was not affected by MT3-MMP expression. Expression of MT3-MMP enhanced Fe65-dependent transactivation by APP fused to the Gal4 DNA-binding and transactivation domains. These results suggest that MT1-MMP, MT3-MMP and MT5-MMP should play an important role in the regulation of APP functions in tissues including the central nervous system. © 2006 The Japanese Biochemical Society. |
| Databáze: | OpenAIRE |
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