The Mitochondrial Protein MAVS Stabilizes p53 to Suppress Tumorigenesis
Wanchuan Zhang,
Jing Gong,
Huan Yang,
Luming Wan,
Yumeng Peng,
Xiaolin Wang,
Jin Sun,
Feng Li,
Yunqi Geng,
Dongyu Li,
Ning Liu,
Gangwu Mei,
Yuan Cao,
Qiulin Yan,
Huilong Li,
Yanhong Zhang,
Xiang He,
Qiaozhi Zhang,
Rui Zhang,
Feixiang Wu,
Hui Zhong,
Congwen Wei
Affiliations
Wanchuan Zhang
Department of Genetic Engineering, Beijing Institute of Biotechnology, Beijing 100850, China; Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, China
Jing Gong
Institute of Physical Science and Information Technology, Anhui University, Hefei 230601, China
Huan Yang
Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, China
Luming Wan
Department of Genetic Engineering, Beijing Institute of Biotechnology, Beijing 100850, China
Yumeng Peng
Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, China
Xiaolin Wang
Department of Genetic Engineering, Beijing Institute of Biotechnology, Beijing 100850, China
Jin Sun
Department of Genetic Engineering, Beijing Institute of Biotechnology, Beijing 100850, China
Feng Li
Department of Genetic Engineering, Beijing Institute of Biotechnology, Beijing 100850, China
Yunqi Geng
Department of Genetic Engineering, Beijing Institute of Biotechnology, Beijing 100850, China
Dongyu Li
Department of Genetic Engineering, Beijing Institute of Biotechnology, Beijing 100850, China
Ning Liu
Department of Genetic Engineering, Beijing Institute of Biotechnology, Beijing 100850, China
Gangwu Mei
Wei Sai Te Biotechnology Company, Beijing, China
Yuan Cao
Department of Laboratory Medicine, The General Hospital of Jinan Military Region, Jinan, Shandong 250031, China
Qiulin Yan
Department of Genetic Engineering, Beijing Institute of Biotechnology, Beijing 100850, China; Institute of Physical Science and Information Technology, Anhui University, Hefei 230601, China
Huilong Li
Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, China
Yanhong Zhang
Department of Genetic Engineering, Beijing Institute of Biotechnology, Beijing 100850, China
Xiang He
Department of Genetic Engineering, Beijing Institute of Biotechnology, Beijing 100850, China
Qiaozhi Zhang
Department of Genetic Engineering, Beijing Institute of Biotechnology, Beijing 100850, China
Rui Zhang
Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, China; Corresponding author
Feixiang Wu
Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, China; Corresponding author
Hui Zhong
Department of Genetic Engineering, Beijing Institute of Biotechnology, Beijing 100850, China; Corresponding author
Congwen Wei
Department of Genetic Engineering, Beijing Institute of Biotechnology, Beijing 100850, China; Corresponding author
Summary: Recent reports have shown the critical role of the mitochondrial antiviral signaling (MAVS) protein in virus-induced apoptosis, but the involvement of MAVS in tumorigenesis is still poorly understood. Herein, we report that MAVS is a key regulator of p53 activation and is critical for protecting against tumorigenesis. We find that MAVS promotes p53-dependent cell death in response to DNA damage. MAVS interacts with p53 and mediates p53 mitochondrial recruitment under genotoxic stress. Mechanistically, MAVS inhibits p53 ubiquitination by blocking the formation of the p53-murine double-minute 2 (MDM2) complex, leading to the stabilization of p53. Notably, compared with their wild-type littermates, MAVS knockout mice display decreased resistance to azoxymethane (AOM) or AOM/dextran sulfate sodium salt (DSS)-induced colon cancer. MAVS expression is significantly downregulated in human colon cancer tissues. These results unveil roles for MAVS in DNA damage response and tumor suppression. : Zhang et al. show that MAVS interacts with p53 and regulates p53-dependent apoptosis, indicating roles for MAVS in tumor suppression and the DNA damage response. Keywords: MAVS, p53, ubiquitination, tumor suppression
