title: RACK1 promotes hepatocellular carcinoma cell survival via CBR1 by suppressing TNF-α-induced ROS generation.
abstract: It has been reported that intracellular accumulation of reactive oxygen species (ROS) has a significant role in tumor necrosis factor (TNF)-α-induced cell apoptosis and necrosis; however, the key molecules regulating ROS generation remain to be elucidated. The present study reports that knockdown of endogenous receptor for activated C kinase 1 (RACK1) increases the intracellular ROS level following TNF-α or H2O2stimulation in human hepatocellular carcinoma (HCC) cells, leading to promotion of cell death. Carbonyl reductase 1 (CBR1), a ubiquitous nicotinamide adenine dinucleotide phosphate-dependent enzyme, is reported to protect cells from ROS-induced cell damage. The present study reports that RACK1 is a regulator of CBR1 that interacts with and sustains the protein stability of CBR1. Overexpression of CBR1 reverses the enhanced cell death due to RACK1 knockdown. Taken together, the results of the present study suggest that RACK1 protects HCC cells from TNF-α-induced cell death by suppressing ROS generation through interacting with and regulating CBR1.
authors.affiliation: Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing 100850, P.R. China; Laboratory of Cellular and Molecular Immunology, Henan University, Kaifeng, Henan 475004, P.R. China.
authors.forename: Silei
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing 100850, P.R. China; Laboratory of Cellular and Molecular Immunology, Henan University, Kaifeng, Henan 475004, P.R. China.
authors.forename: Huanling
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing 100850, P.R. China; Laboratory of Cellular and Molecular Immunology, Henan University, Kaifeng, Henan 475004, P.R. China.
authors.forename: Yawei
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing 100850, P.R. China.
authors.forename: Xinying
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing 100850, P.R. China.
authors.forename: Jiyan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing 100850, P.R. China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Hou
authors.affiliation: Laboratory of Cellular and Molecular Immunology, Henan University, Kaifeng, Henan 475004, P.R. China.
authors.forename: Yuanfang
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing 100850, P.R. China.
authors.forename: Qingyang
authors.initials: Q
authors.lastname: Wang
keywords: carbonyl reductase 1; cell death; hepatocellular carcinoma; reactive oxygen species; receptor for activated C kinase 1; tumor necrosis factor-α