RGD Reference Report - Dexras1 interacts with FE65 to regulate FE65-amyloid precursor protein-dependent transcription. - Rat Genome Database

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Dexras1 interacts with FE65 to regulate FE65-amyloid precursor protein-dependent transcription.

Authors: Lau, KF  Chan, WM  Perkinton, MS  Tudor, EL  Chang, RC  Chan, HY  McLoughlin, DM  Miller, CC 
Citation: Lau KF, etal., J Biol Chem. 2008 Dec 12;283(50):34728-37. doi: 10.1074/jbc.M801874200. Epub 2008 Oct 15.
RGD ID: 8553468
Pubmed: PMID:18922798   (View Abstract at PubMed)
PMCID: PMC3259905   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M801874200   (Journal Full-text)

FE65 is an adaptor protein that binds to and forms a transcriptionally active complex with the gamma-secretase-derived amyloid precursor protein (APP) intracellular domain. The regulatory mechanisms of FE65-APP-mediated transcription are still not clear. In this report, we demonstrate that Dexras1, a Ras family small G protein, binds to FE65 PTB2 domain and potently suppresses the FE65-APP-mediated transcription. The suppression is not via competition for binding of FE65 between Dexras1 and APP because the two proteins can simultaneously bind to the FE65 PTB2 domain. Phosphorylation of FE65 tyrosine 547 within the PTB2 domain has been shown to enhance FE65-APP-mediated transcription but not to influence binding to APP. Here we find that this phosphorylation event reduces the binding between Dexras1 and FE65. We also demonstrate that Dexras1 inhibits the FE65-APP-mediated transcription of glycogen synthase kinase 3beta (GSK3 beta). Moreover, small interfering RNA knockdown of Dexras1 enhances GSK3 beta expression and increases phosphorylation of Tau, a GSK3 beta substrate. Thus, Dexras1 functions as a suppressor of FE65-APP-mediated transcription, and FE65 tyrosine 547 phosphorylation enhances FE65-APP-mediated transcription, at least in part, by modulating the interaction between FE65 and Dexras1. These findings reveal a novel regulatory mechanism for FE65-APP-mediated signaling.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of DNA-templated transcription involved_inIMP 8553468PMID:18922798UniProt 
positive regulation of DNA-templated transcription involved_inIDA 8553468PMID:18922798UniProt 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cytoplasm located_inIDA 8553468; 8553468PMID:18922798UniProt 
nucleus located_inIDA 8553468; 8553468PMID:18922798UniProt 
perinuclear region of cytoplasm located_inIDA 8553468PMID:18922798UniProt 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding enablesIPIUniProtKB:Q9JKF88553468PMID:18922798UniProt 
protein binding enablesIPIUniProtKB:P469338553468PMID:18922798UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Apbb1  (amyloid beta precursor protein binding family B member 1)
Rasd1  (ras related dexamethasone induced 1)


Additional Information