BACE1 gene expression and protein degradation.

Abstract:

:Deposition of amyloid beta protein in the brain is the major pathological feature of Alzheimer's disease. Amyloid beta protein is generated from beta-amyloid precursor protein by beta-secretase and gamma-secretase. Proteolytic processing of amyloid precursor protein at the beta site by BACE1 is essential to generate amyloid beta protein. BACE1, the major beta-secretase involved in cleaving amyloid precursor protein, has been identified as a type 1 membrane-associated aspartyl protease. In this study, we found that BACE1 gene expression is controlled by a TATA-less promoter. BACE1 gene expression is tightly regulated at the transcriptional level and the transcription factor Sp1 plays an important role in regulation of BACE1 to process amyloid precursor protein generating amyloid beta protein. Furthermore, we found that BACE1 protein is ubiquitinated, and the degradation of BACE1 proteins and amyloid precursor protein processing are regulated by the ubiquitin-proteasome pathway.

journal_name

Ann N Y Acad Sci

authors

Zhou W,Qing H,Tong Y,Song W

doi

10.1196/annals.1332.004

subject

Has Abstract

pub_date

2004-12-01 00:00:00

pages

49-67

eissn

0077-8923

issn

1749-6632

pii

1035/1/49

journal_volume

1035

pub_type

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