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논문 기본 정보

자료유형
학술저널
저자정보
Nam, Miyoung (Department of New Drug Discovery and Development, Chungnam National University) Kim, Cheol-Hee (Department of Biology, Chungnam National University) Kim, Dong-Uk (Aging Research Center, Korea Research Institute of Bioscience and Biotechnology [KRIBB]) Lee, Sook-Jeong (Department of New Drug Discovery and Development, Chungnam National University) Hoe, Kwang-Lae (Department of New Drug Discovery and Development, Chungnam National University)
저널정보
한국응용생명화학회 Applied Biological Chemistry Applied Biological Chemistry 제59권 제4호
발행연도
2016.1
수록면
543 - 551 (9page)

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Hepatitis C virus (HCV) non-structural 5A (NS5A) protein is associated with a wide variety of host signaling pathways by binding to C-terminal polyproline (PxxP) motifs of various proteins. In this study, we used yeast two-hybrid analysis and a GST pull-down assay to screen a novel NS5A interacting protein and elucidate the binding site and cellular signaling by focusing on recombinant human epidermal growth factor (rhEGF)-mediated ERK1/2 activation. Screening a liver cDNA library revealed that h-prune, a member of the DHH (Asp-His-His) protein superfamily, directly interacted with HCV NS5A C-terminus. In particular, a mutation of five proline amino acids to alanine in this region revealed that these two proteins produced strong interaction through this domain. It is known that h-prune possesses a highly conserved DHH motif, which has exopolyphosphatase activity that accelerates hydrolysis of inorganic polyphosphate. A time-chasing analysis after rhEGF treatment demonstrated that h-prune overexpression almost restored NS5A-mediated attenuation of ERK1/2 phosphorylation, but h-prune itself did not alter this signaling. Although the detailed mechanisms need to be clarified, this study demonstrates that h-prune interacts directly with the PxxP motif of the HCV NS5A C-terminus and that this binding alters the rhEGF-mediated ERK1/2 signaling cascade in liver cells.

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