التفاصيل البيبلوغرافية
| العنوان: |
Translational regulation of BACE-1 expression in neuronal and non-neuronal cells |
| المؤلفون: |
Davide De, Pietri Tonelli, Marija Mihailovich, Ra Di Cesare, Franca Codazzi, Fabio Grohovaz, Daniele Zacchetti |
| المساهمون: |
The Pennsylvania State University CiteSeerX Archives |
| المصدر: |
http://nar.oxfordjournals.org/content/32/5/1808.full.pdfTest. |
| سنة النشر: |
2003 |
| المجموعة: |
CiteSeerX |
| الوصف: |
As the main beta-secretase of the central nervous system, BACE-1 is a key protein in the pathogenesis of Alzheimer's disease. Excessive expression of the protein might cause an overproduction of the neuro-toxic beta-amyloid peptide. Therefore, a tight regula-tion of BACE-1 expression is expected in vivo. In addition to a possible transcriptional control, the BACE-1 transcript leader contains features that might constitute mechanisms of translational regu-lation of protein expression. Moreover, recent work has revealed an increase of BACE-1 protein and beta-secretase activity in some Alzheimer's disease patients, although a corresponding increase of tran-script has not been reported. Here we show that BACE-1 translation could be modulated at multiple stages. The presence of several upstream ATGs strongly reduces the translation of the main open reading frame. This inhibition could be overcome with conditions that favour skipping of upstream ATGs. We also report an alternative splicing of the BACE-1 transcript leader that reduces the number of upstream ATGs. Finally, we show that translation driven by the BACE-1 transcript leader is increased in activated astrocytes independently of the splicing event, indicating yet another mechanism of transla-tional control. Our ®ndings might explain why increases in BACE-1 protein or activity are reported in the brain of Alzheimer's disease patients even in the absence of changes in transcript levels. |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| العلاقة: |
http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.558.884Test; http://nar.oxfordjournals.org/content/32/5/1808.full.pdfTest |
| الإتاحة: |
http://nar.oxfordjournals.org/content/32/5/1808.full.pdfTest |
| حقوق: |
Metadata may be used without restrictions as long as the oai identifier remains attached to it. |
| رقم الانضمام: |
edsbas.B2BB30C3 |
| قاعدة البيانات: |
BASE |
