JBC：一信号传递蛋白与丙型肝炎病毒复制有关
研究人员最近发现一种抑制丙型肝炎病毒复制的蛋白，为研发治疗丙型肝炎的新药提供了参考。
丙型肝炎是一种血源性传染病，有引发肝硬化和肝癌的可能。病毒通过复制和抑制宿主体内各种抗病毒蛋白，在宿主体内传播。研究人员希望弄清这两个机制，抑制病毒复制、停止病毒传播。
p21-活化蛋白激酶1（p21-activated kinase 1）是一种在许多细胞信号传递途径中扮演重要角色的蛋白，以前人们不知道其与调节丙型肝炎复制有关。Stanley M. Lemon等最近发现，这种蛋白能够抑制病毒复制。
原始出处:
J. Biol. Chem., Vol. 282, Issue 16, 11836-11848, April 20, 2007
p21-activated Kinase 1 Is Activated through the Mammalian Target of Rapamycin/p70 S6 Kinase Pathway and Regulates the Replication of Hepatitis C Virus in Human Hepatoma Cells*
Hisashi Ishida, Kui Li, MinKyung Yi, and Stanley M. Lemon1
From the Center for Hepatitis Research, Institute for Human Infections and Immunity, and the Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 77555-1018
Abstract
Cellular mechanisms that regulate the replication of hepatitis C virus (HCV) RNA are poorly understood. p21-activated kinase 1 (PAK1) is a serine/threonine kinase that has been suggested to participate in antiviral signaling. We studied its role in the cellular control of HCV replication. Transfection of PAK1-specific small interfering RNA enhanced viral RNA and protein abundance in established replicon cell lines as well as cells infected with chimeric genotype 1a/2a HCV, despite reducing cellular proliferation, suggesting specific regulation of HCV replication. PAK1 knockdown did not reduce interferon regulatory factor 3-dependent gene expression, indicating that this regulation is independent of the retinoic acid-inducible gene I/interferon regulatory factor 3 pathway. On the other hand, LY294002 and rapamycin abolished PAK1 phosphorylation and enhanced HCV abundance, suggesting that the mammalian target of rapamycin (mTOR) is involved in PAK1 regulation of HCV. Small interfering RNA knockdown of the mTOR substrate p70 S6 kinase abrogated PAK1 phosphorylation and enhanced HCV RNA abundance, whereas overexpression of a constitutively active alternate substrate, eukaryotic translation initiation factor 4E-binding protein 1, increased cap-independent viral translation and viral RNA abundance without influencing PAK1 phosphorylation. Similar data indicated that mTOR is regulated by both phosphatidylinositol 3-kinase/Akt and ERK. Taken together, the data indicate that p70 S6 kinase activates PAK1 and contributes to phosphatidylinositol 3-kinase- and ERK-mediated regulation of HCV RNA replication.
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