کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10754237 | 1050353 | 2014 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Design of a PROTAC that antagonizes and destroys the cancer-forming X-protein of the hepatitis B virus
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کلمات کلیدی
PRBoxygen-dependent degradationX-proteinPROTACVHLHIFSCFCPPHCC - HCCamino acid - آمینو اسیدvon Hippel-Lindau - از Hippel-LindauApoptosis - خزان یاختهایHypoxia-inducible factor - فاکتور القاء کننده هیپوکسیODD - فردHBV - هپاتیت بhepatitis B virus - ویروس هپاتیت بیretinoblastoma protein - پروتئین رتینوبلاستوماCell-penetrating peptide - پپتید نفوذ سلولیHepatocellular carcinoma - کارسینوم هپاتوسلولار(کارسینوم سلولهای استخوانی)
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Design of a PROTAC that antagonizes and destroys the cancer-forming X-protein of the hepatitis B virus Design of a PROTAC that antagonizes and destroys the cancer-forming X-protein of the hepatitis B virus](/preview/png/10754237.png)
چکیده انگلیسی
The X-protein of the hepatitis B virus (HBV) is essential for virus infection and contributes to the development of HBV-induced hepatocellular carcinoma (HCC), a disease which causes more than one million deaths each year. Here we describe the design of a novel PROTAC (proteolysis targeting chimeric molecule) capable of simultaneously inducing the degradation of the X-protein, and antagonizing its function. The PROTAC was constructed by fusing the N-terminal oligomerization and C-terminal instability domains of the X-protein to each other, and rendering them cell-permeable by the inclusion of a polyarginine cell-penetrating peptide (CPP). It was predicted that the oligomerization domain would bind the X-protein, and that the instability domain would cause the X-protein to be targeted for proteasomal degradation. Addition of the PROTAC to HepG2 liver cancer cells, engineered to express full-length and C-terminally truncated forms of the X-protein, resulted in the degradation of both forms of the X-protein. A cell-permeable stand-alone form of the oligomerization domain was taken up by HepG2 cells, and acted as a dominant-negative inhibitor, causing inhibition of X-protein-induced apoptosis. In summary, the PROTAC described here induces the degradation of the X-protein, and antagonizes its function, and warrants investigation in a preclinical study for its ability to prevent or treat HBV infection and/or the development of HCC.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 453, Issue 4, 31 October 2014, Pages 735-740
Journal: Biochemical and Biophysical Research Communications - Volume 453, Issue 4, 31 October 2014, Pages 735-740
نویسندگان
Kristopher Montrose, Geoffrey W. Krissansen,