Deubiquitinase OTUD6A Regulates Innate Immune Response via Targeting UBC13
Zhiwei Li,
Guanwen Li,
Yunfei Li,
Yujie Luo,
Yuhan Jiang,
Ziyu Zhang,
Ziyi Zhou,
Shengde Liu,
Chen Wu,
Fuping You
Affiliations
Zhiwei Li
College of Life Sciences, Hebei University, Baoding 071002, China
Guanwen Li
College of Life Sciences, South China Agricultural University, Guangzhou 510642, China
Yunfei Li
Department of Systems Biomedicine, Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
Yujie Luo
Department of Systems Biomedicine, Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
Yuhan Jiang
College of Life Sciences, Hebei University, Baoding 071002, China
Ziyu Zhang
College of Life Sciences, Hebei University, Baoding 071002, China
Ziyi Zhou
College of Life Sciences, Hebei University, Baoding 071002, China
Shengde Liu
Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing 100142, China
Chen Wu
College of Life Sciences, Hebei University, Baoding 071002, China
Fuping You
Department of Systems Biomedicine, Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
OTUD6A is a deubiquitinase that plays crucial roles in various human diseases. However, the precise regulatory mechanism of OTUD6A remains unclear. In this study, we found that OTUD6A significantly inhibited the production of type I interferon. Consistently, peritoneal macrophages and bone marrow-derived macrophages from Otud6a−/− mice produced more type I interferon after virus infection compared to cells from WT mice. Otud6a−/−− mice also exhibited increased resistance to lethal HSV-1 and VSV infections, as well as LPS attacks due to decreased inflammatory responses. Mechanistically, mass spectrometry results revealed that UBC13 was an OTUD6A-interacting protein, and the interaction was significantly enhanced after HSV-1 stimulation. Taken together, our findings suggest that OTUD6A plays a crucial role in the innate immune response and may serve as a potential therapeutic target for infectious disease.
