Raf-1 kinase associates with Hepatitis C virus NS5A and regulates viral replication

被引：67

作者：

Bürckstümmer, T

Kriegs, M

Lupberger, J

Pauli, EK

Schmittel, S

Hildt, E

机构：

[1] Robert Koch Inst, D-13353 Berlin, Germany

[2] Humboldt Univ, Charite, Inst Virol, D-10115 Berlin, Germany

[3] Univ Freiburg, Dept Med 2, D-79106 Freiburg, Germany

来源：

FEBS LETTERS | 2006年 / 580卷 / 02期

关键词：

HCV; NS5A; Raf-1; replication;

D O I：

10.1016/j.febslet.2005.12.071

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

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 replication. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

收藏

页码：575 / 580

页数：6

相关论文

共 23 条

[1]

Efficient initiation of HCV RNA replication in cell culture [J].

Blight, KJ ;

Kolykhalov, AA ;

Rice, CM .

SCIENCE, 2000, 290 (5498) :1972-1974

[2]

An amino-terminal amphipathic α-helix mediates membrane association of the hepatitis C virus nonstructural protein 5A [J].

Brass, V ;

Bieck, E ;

Montserret, R ;

Wölk, B ;

Hellings, JA ;

Blum, HE ;

Penin, F ;

Moradpour, D .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (10) :8130-8139

[3]

SERUM-INDUCED, TPA-INDUCED, AND RAS-INDUCED EXPRESSION FROM AP-1/ETS-DRIVEN PROMOTERS REQUIRES RAF-1 KINASE [J].

BRUDER, JT ;

HEIDECKER, G ;

RAPP, UR .

GENES & DEVELOPMENT, 1992, 6 (04) :545-556

[4]

Hepatitis C virus RNA replication is resistant to tumour necrosis factor-α [J].

Frese, M ;

Barth, K ;

Kaul, A ;

Lohmann, V ;

Schwärzle, V ;

Bartenschlager, R .

JOURNAL OF GENERAL VIROLOGY, 2003, 84 :1253-1259

[5]

Interactions between viral nonstructural proteins and host protein hVAP-33 mediate the formation of hepatitis C virus RNA replication complex on lipid raft [J].

Gao, L ;

Aizaki, H ;

He, JW ;

Lai, MMC .

JOURNAL OF VIROLOGY, 2004, 78 (07) :3480-3488

[6]

Identification of the hepatitis C virus RNA replication complex in Huh-7 cells harboring subgenomic replicons [J].

Gosert, R ;

Egger, D ;

Lohmann, V ;

Bartenschlager, R ;

Blum, HE ;

Bienz, K ;

Moradpour, D .

JOURNAL OF VIROLOGY, 2003, 77 (09) :5487-5492

[7]

Subversion of cell signaling pathways by hepatitis C virus nonstructural 5A protein via interaction with Grb2 and P85 phosphatidylinositol 3-kinase [J].

He, YP ;

Nakao, HH ;

Tan, SL ;

Polyak, PJ ;

Neddermann, P ;

Vijaysri, S ;

Jacobs, BL ;

Katze, MG .

JOURNAL OF VIROLOGY, 2002, 76 (18) :9207-9217

[8]

PROTEOLYTIC PROCESSING AND MEMBRANE ASSOCIATION OF PUTATIVE NONSTRUCTURAL PROTEINS OF HEPATITIS-C VIRUS [J].

HIJIKATA, M ;

MIZUSHIMA, H ;

TANJI, Y ;

KOMODA, Y ;

HIROWATARI, Y ;

AKAGI, T ;

KATO, N ;

KIMURA, K ;

SHIMOTOHNO, K .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (22) :10773-10777

[9]

The PreS2 activator MJBst of hepatitis B virus activates c-raf-1/Erk2 signaling in transgenic mice [J].

Hildt, E ;

Munz, B ;

Saher, G ;

Reifenberg, K ;

Hofschneider, PH .

EMBO JOURNAL, 2002, 21 (04) :525-535

[10]

Identification of Grb2 as a novel binding partner of tumor necrosis factor (TNF) receptor I [J].

Hildt, E ;

Oess, S .

JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 189 (11) :1707-1714