Raf‐1 kinase associates with Hepatitis C virus NS5A and regulates viral replication
- 29 December 2005
- journal article
- Published by Wiley in FEBS Letters
- Vol. 580 (2), 575-580
- https://doi.org/10.1016/j.febslet.2005.12.071
Abstract
Hepatitis C virus (HCV) is a positive-strand RNA virus that frequently causes persistent infection associated with severe liver disease. HCV nonstructural protein 5A (NS5A) is essential for viral replication. Here, the kinase Raf-1 was identified as a novel cellular binding partner of NS5A, binding to the C-terminal domain of NS5A. Raf-1 colocalizes with NS5A in the HCV replication complex. The interaction of NS5A with Raf-1 results in increased Raf-1 phosphorylation at serine 338. Integrity of Raf-1 is crucial for HCV replication: inhibition of Raf-1 by the small-molecule inhibitor BAY43-9006 or downregulation of Raf-1 by siRNA attenuates viral replicationKeywords
This publication has 23 references indexed in Scilit:
- p21-activated Kinase 1 (Pak1)-dependent Phosphorylation of Raf-1 Regulates Its Mitochondrial Localization, Phosphorylation of BAD, and Bcl-2 AssociationPublished by Elsevier ,2005
- Structure and Function of the Membrane Anchor Domain of Hepatitis C Virus Nonstructural Protein 5AJournal of Biological Chemistry, 2004
- Mechanism of Activation of the RAF-ERK Signaling Pathway by Oncogenic Mutations of B-RAFCell, 2004
- The Hepatitis C Virus Non-structural NS5A Protein Inhibits Activating Protein–1 Function by Perturbing Ras-ERK Pathway SignalingJournal of Biological Chemistry, 2003
- Hepatitis C virus RNA replication is resistant to tumour necrosis factor-αJournal of General Virology, 2003
- An Amino-terminal Amphipathic α-Helix Mediates Membrane Association of the Hepatitis C Virus Nonstructural Protein 5AJournal of Biological Chemistry, 2002
- Microtubule Integrity Regulates Pak Leading to Ras-independent Activation of Raf-1Journal of Biological Chemistry, 2001
- Efficient Initiation of HCV RNA Replication in Cell CultureScience, 2000
- Replication of Subgenomic Hepatitis C Virus RNAs in a Hepatoma Cell LineScience, 1999
- Serum-, TPA-, and Ras-induced expression from Ap-1/Ets-driven promoters requires Raf-1 kinase.Genes & Development, 1992