Cleavage of amyloid-β precursor protein (APP) by membrane-type matrix metalloproteinases
Bibliographic Information
- Other Title
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- Cleavage of Amyloid ベータ Precursor Protein APP by Membrane Type Matrix Metalloproteinases
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Abstract
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.
Journal
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- Journal of Biochemistry
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Journal of Biochemistry 139 (3), 517-526, 2006-03-01
日本生化学会 = Japanese Biochemical Society
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Keywords
Details 詳細情報について
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- CRID
- 1390294496044131200
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- NII Article ID
- 10018846859
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- NII Book ID
- AA00694073
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- ISSN
- 0021924X
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- NDL BIB ID
- 7878792
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- Text Lang
- en
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- Data Source
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- JaLC
- IRDB
- NDL
- CiNii Articles