کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1931409 1050551 2010 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Hepatitis C virus nonstructural protein-5A activates sterol regulatory element-binding protein-1c through transcription factor Sp1
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Hepatitis C virus nonstructural protein-5A activates sterol regulatory element-binding protein-1c through transcription factor Sp1
چکیده انگلیسی

Steatosis is an important clinical manifestation of hepatitis C virus (HCV) infection. The molecular mechanisms of HCV-associated steatosis are not well understood. Sterol regulatory element-binding protein-1c (SREBP-1c) is a key transcription factor which activates the transcription of lipogenic genes. Here we showed that the nuclear, mature SREBP-1c level increases in the nucleus of replicon cells expressing HCV-3a nonstructural protein-5A (NS5A). We further showed that HCV-3a NS5A up-regulates SREBP-1c transcription. Additional analysis showed that transcriptional factor Sp1 is involved in SREBP-1c activation by HCV-3a NS5A because inhibition of Sp1 activity by mithramycin A or a dominant-negative Sp1 construct abrogated SREBP-1c promoter activation by HCV-3a NS5A. In addition, chromatin immunoprecipitation (ChIP) assay demonstrated enhanced binding of Sp1 on the SREBP-1c promoter in HCV-3a NS5A replicon cells. These results showed that HCV-3a NS5A activates SREBP-1c transcription through Sp1. Taken together, our results suggest that HCV-3a NS5A is a contributing factor for steatosis caused by HCV-3a infection.

Research highlights
► A chimeric subgenomic HCV replicon expresses HCV-3a NS5A in an HCV-1b backbone.
► HCV-3a NS5A increases mature SREBP-1c protein level.
► HCV-3a NS5A activates SREBP-1c transcription.
► Domain II of HCV-3a NS5A is more effective in SREBP-1c promoter activation.
► Transcription factor Sp1 is required for SREBP-1c activation by HCV-3a NS5A.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 402, Issue 3, 19 November 2010, Pages 549–553
نویسندگان
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