کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8941298 | 1644994 | 2018 | 30 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Neuregulin 1 discovered as a cleavage target for the HCV NS3/4A protease by a microfluidic membrane protein array
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کلمات کلیدی
AP-MSMAVSRTKRIG-ITBK1IIRNRG1neuregulin1TRAFMPAY2HTC-PTPPDMSEGFRHCC - HCCPCA - PCATRIF - Trif بهProtein complementation assay - آزمایش تکمیلی پروتئینTnT - تی ان تیTIR - تیرtumor necrosis factor receptor associated factor - عوامل مرتبط با گیرنده فاکتور نکروز تومورnonstructural protein - غلظت پروتئینYeast-two hybrid - مخمر دو مخلوطHepatitis C virus - هپاتیت سیHCV - هپاتیت سیInnate immune response - پاسخ ایمنی ذاتیPolydimethylsiloxane - پلیمتیلسیلوکسانHepatocellular carcinoma - کارسینوم هپاتوسلولار(کارسینوم سلولهای استخوانی)Receptor Tyrosine Kinase - گیرنده تیروزین کینازEpidermal growth factor receptor - گیرنده فاکتور رشد اپیدرمال
موضوعات مرتبط
مهندسی و علوم پایه
مهندسی شیمی
بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The hepatitis C virus (HCV) non-structural protein 3 (NS3) is essential for HCV maturation. The NS3/4A protease is a target for several HCV treatments and is a well-known target for HCV drug discovery. The protein is membrane associated and thus probably interacts with other membrane proteins. However, the vast majority of known NS3 host partners are soluble proteins rather than membrane proteins, most likely due to lack of appropriate platforms for their discovery. Utilization of an integrated microfluidics platform enables analysis of membrane proteins in their native form. We screened over 2800 membrane proteins for interaction with NS3 and 90 previously unknown interactions were identified. Of these, several proteins were selected for validation by co-immunoprecipitation and for NS3 proteolytic activity. Bearing in mind the considerable number of interactions formed, together with the popularity of NS3/4A protease as a drug target, it was striking to note its lack of proteolytic activity. Only a single protein, Neuregulin1, was observed to be cleaved, adding to the 3 known NS3/4A cleavage targets. Neuregulin1 participates in neural proliferation. Recent studies have shown its involvement in HCV infection and hepatocellular carcinoma. We showed that NS3/4A triggers an increase in neuregulin1 mRNA levels in HCV infected cells. Despite this increase, its protein concentration is decreased due to proteolytic cleavage. Additionally, its EGF-like domain levels were increased, possibly explaining the ErbB2 and EGFR upregulation in HCV infected cells. The newly discovered protein interactions may provide insights into HCV infection mechanisms and potentially provide new therapeutic targets against HCV.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: New Biotechnology - Volume 45, 25 October 2018, Pages 113-122
Journal: New Biotechnology - Volume 45, 25 October 2018, Pages 113-122
نویسندگان
Nika Schwartz, Michal Pellach, Yair Glick, Reuven Gil, Gahl Levy, Dorit Avrahami, Efrat Barbiro-Michaely, Yaakov Nahmias, Doron Gerber,