کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3430973 1594405 2007 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Hepatitis B virus X protein (HBx) activates ATF6 and IRE1-XBP1 pathways of unfolded protein response
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ویروس شناسی
پیش نمایش صفحه اول مقاله
Hepatitis B virus X protein (HBx) activates ATF6 and IRE1-XBP1 pathways of unfolded protein response
چکیده انگلیسی

Numerous viruses including hepatitis B virus (HBV) induce endoplasmic reticulum (ER) stress, which interrupts protein folding causing accumulation of unfolded or misfolded proteins in ER. To alleviate the stress placed on ER, these proteins must be refolded or degraded by activating a specific cellular response known as ER stress response or unfolded protein response (UPR). Two UPR-specific signaling pathways involving transmembrane proteins ATF6 and XBP1 generate critical transcription factors that activate UPR-responsive genes. In this study, the role of the multifunctional regulatory protein of HBV (HBx protein) in activation of UPR was investigated. In Hep3B cells with transit or stable expression of HBx, XBP1 expression and ATF6 cleavage was observed, suggesting that the ATF6 and IRE1-XBP1 pathways were activated. Furthermore, these two pathways were also activated in HepG2.2.15 cells that constitutively replicate the intact HBV genome, and blocked at least partly by cotransfection with small interfering RNA (siRNA) expression plasmid that knocked down HBx expression. Our results clearly establish HBx as an inducer of UPR and the activator of the ATF6 and IRE1-XBP1 pathways of UPR. HBx-mediated activation of these pathways of UPR probably promote HBV replication and expression in liver cells, and contribute to liver pathogenesis, perhaps even to hepatocellular carcinoma (HCC) development.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Virus Research - Volume 124, Issues 1–2, March 2007, Pages 44–49
نویسندگان
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