The upstream stimulatory factor functionally interacts with the Alzheimer amyloid beta-protein precursor gene.
The upstream stimulatory factor functionally interacts with the Alzheimer amyloid beta-protein precursor gene.
复制标题
上游刺激因子与阿尔茨海默淀粉样β蛋白前体基因发生功能性相互作用。
DOI：
10.1093/hmg/4.9.1527
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发表时间：
1995
影响因子：
3.5
通讯作者：
Tanzi,RE
中科院分区：
文献类型：
--
作者：
Kovacs,DM;Wasco,W;Witherby,J;Felsenstein,KM;Brunel,F;Roeder,RG;Tanzi,RE
The amyloid β-protein precursor (APP) gives rise to the Aβ peptide, which is deposited in the brains of patients with Alzheimer's disease and Down's syndrome. Overexpression of APP due to a third copy of the gene appears to correlate with very early onset of Alzheimer's disease neuropathology in the brains of Down's syndrome patients. Thus, the identification of the factors involved with transcriptional regulation of the APP gene could provide critical clues regarding the events leading to the formation of amyloid deposits. An overlapping AP-1/AP-4 site in the proximal promoter region (-39 to-49) of the human APP gene has previously been shown to increase transcription 4-fold. Here we identify the factor binding specifically to this element as the upstream stimulatory factor USF, unrelated to the c-fos/c-jun complex or the AP-4 factor.In vitrotranscription and co-transfection studies show that USF activates transcription from the APP promoter and that the AP-1/AP-4 element participates in this activation. Modulation of APP expression via regulation of USF could potentially ameliorate the production of Alzheimer-augmented β-amyloid.
