RGD Reference Report - APP-BP1 mediates APP-induced apoptosis and DNA synthesis and is increased in Alzheimer's disease brain. - Rat Genome Database

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APP-BP1 mediates APP-induced apoptosis and DNA synthesis and is increased in Alzheimer's disease brain.

Authors: Chen, Y  Liu, W  McPhie, DL  Hassinger, L  Neve, RL 
Citation: Chen Y, etal., J Cell Biol. 2003 Oct 13;163(1):27-33.
RGD ID: 2302388
Pubmed: PMID:14557245   (View Abstract at PubMed)
PMCID: PMC2173435   (View Article at PubMed Central)
DOI: DOI:10.1083/jcb.200304003   (Journal Full-text)

APP-BP1, first identified as an amyloid precursor protein (APP) binding protein, is the regulatory subunit of the activating enzyme for the small ubiquitin-like protein NEDD8. We have shown that APP-BP1 drives the S- to M-phase transition in dividing cells, and causes apoptosis in neurons. We now demonstrate that APP-BP1 binds to the COOH-terminal 31 amino acids of APP (C31) and colocalizes with APP in a lipid-enriched fraction called lipid rafts. We show that coexpression of a peptide representing the domain of APP-BP1 that binds to APP, abolishes the ability of overexpressed APP or the V642I mutant of APP to cause neuronal apoptosis and DNA synthesis. A dominant negative mutant of the NEDD8 conjugating enzyme hUbc12, which participates in the ubiquitin-like pathway initiated by APP-BP1, blocks neuronal apoptosis caused by APP, APP(V642I), C31, or overexpression of APP-BP1. Neurons overexpressing APP or APP(V642I) show increased APP-BP1 protein levels in lipid rafts. A similar increase in APP-BP1 in lipid rafts is observed in the Alzheimer's disease brain hippocampus, but not in less-affected areas of Alzheimer's disease brain. This translocation of APP-BP1 to lipid rafts is accompanied by a change in the subcellular localization of the ubiquitin-like protein NEDD8, which is activated by APP-BP1.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Alzheimer's disease  IEP 2302388 RGD 
Alzheimer's disease  ISONAE1 (Homo sapiens)2302388; 2302388 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of neuron apoptotic process  IMP 2302388 RGD 
response to organic cyclic compound  IDA 2302388 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nae1  (NEDD8 activating enzyme E1 subunit 1)
Nedd8  (NEDD8 ubiquitin like modifier)
Ube2m  (ubiquitin-conjugating enzyme E2M)

Genes (Mus musculus)
Nae1  (NEDD8 activating enzyme E1 subunit 1)

Genes (Homo sapiens)
NAE1  (NEDD8 activating enzyme E1 subunit 1)

Objects referenced in this article
Gene App amyloid beta precursor protein Rattus norvegicus

Additional Information