Source:http://linkedlifedata.com/resource/pubmed/id/14970212
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
18
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pubmed:dateCreated |
2004-4-26
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pubmed:abstractText |
Amyloid precursor protein (APP) processing is of major interest in Alzheimer's disease research, since sequential cleavages by beta- and gamma-secretase lead to the formation of the 4-kDa amyloid Abeta protein peptide that accumulates in Alzheimer's disease brain. The processing of APP involves proteolytic conversion by different secretases leading to alpha-, beta-, gamma-, delta-, and epsilon-cleavages. Since modulation of these cleavages represents a rational therapeutic approach to control amyloid formation, its interference with the processing of the members of the APP gene family is of considerable importance. By using C-terminally tagged constructs of APLP-1 and APLP-2 and the untagged proteins, we have characterized their proteolytic C-terminal fragments produced in stably transfected SH-SY5Y cells. Pharmacological manipulation with specific protease inhibitors revealed that both homologues are processed by alpha- and gamma-secretase-like cleavages, and that their intracellular domains can be released by cleavage at epsilon-sites. APLP-2 processing appears to be the most elaborate and to involve alternative cleavage sites. We show that APLP-1 is the only member of the APP gene family for which processing can be influenced by N-glycosylation. Additionally, we were able to detect p3-like fragments of APLP-1 and p3-like and Abeta-like fragments of APLP-2 in the media of stably transfected SH-SY5Y cells.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/APLP1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/APLP2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid Precursor Protein Secretases,
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid beta-Protein Precursor,
http://linkedlifedata.com/resource/pubmed/chemical/Aspartic Acid Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/BACE1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Protease Inhibitors
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
30
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
18146-56
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:14970212-Amyloid Precursor Protein Secretases,
pubmed-meshheading:14970212-Amyloid beta-Protein Precursor,
pubmed-meshheading:14970212-Aspartic Acid Endopeptidases,
pubmed-meshheading:14970212-Binding Sites,
pubmed-meshheading:14970212-Cell Line,
pubmed-meshheading:14970212-Endopeptidases,
pubmed-meshheading:14970212-Glycosylation,
pubmed-meshheading:14970212-Humans,
pubmed-meshheading:14970212-Multigene Family,
pubmed-meshheading:14970212-Nerve Tissue Proteins,
pubmed-meshheading:14970212-Peptide Fragments,
pubmed-meshheading:14970212-Protease Inhibitors,
pubmed-meshheading:14970212-Protein Processing, Post-Translational,
pubmed-meshheading:14970212-Transfection
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pubmed:year |
2004
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pubmed:articleTitle |
The proteolytic processing of the amyloid precursor protein gene family members APLP-1 and APLP-2 involves alpha-, beta-, gamma-, and epsilon-like cleavages: modulation of APLP-1 processing by n-glycosylation.
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pubmed:affiliation |
Zentrum für Molekulare Biologie Heidelberg, ZMBH, INF 282, 69120 Heidelberg, Germany. s.eggert@zmbh.uni-heidelberg.de
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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