Deubiquitinating enzyme OTUB1 in immunity and cancer: Good player or bad actor?

• Published in: Cancer letters 2022-02, Vol.526, p.248-258
• Main Authors: Liao, Yihao, Yang, Mengyue, Wang, Keke, Wang, Youzhi, Zhong, Boqiang, Jiang, Ning
• Format: Article
• Language: English
• Subjects: Animals; Autoimmune diseases; Bladder cancer; Breast cancer; Cancer; Carcinogenesis; CD8 antigen; CD8-Positive T-Lymphocytes - enzymology; CD8-Positive T-Lymphocytes - immunology; Cell activation; Colorectal cancer; Cytokines; Deubiquitinating Enzymes - metabolism; DNA damage; DNA repair; Enzymes; Esophageal cancer; Humans; Immunity; Immunological diseases; Inflammation; Kinases; Lymphocytes T; Medical prognosis; Metastasis; Neoplasms - enzymology; Neoplasms - immunology; OTUB1; Ovaries; PD-L1 protein; Phosphorylation; Proteins; Regulation; Therapeutic targets; Treatment; Ubiquitin
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2021.12.002

OTU domain-containing ubiquitin aldehyde-binding proteins 1 (OTUB1) is the most important element of the deubiquitinase OTU superfamily, which has been identified as an essential regulator of diverse physiological processes, such as DNA damage repair and cytokines secretion. Recently, we found that the pro-carcinogenesis role of OTUB1 and the relationship between OTUB1 and immune response have gradually become the research hot-spot. OTUB1 regulates NK/CD8 T cell activation, autoimmune diseases, PD-L1 mediated immune evasion, viral or bacterial infection related immune response and the occurrence and progression of various cancers via deubiquitinating and stabilizing related proteins. This review provides a comprehensive description about the role and regulatory axis of OTUB1. We can explore the balance between immune response and defense via regulating the level of OTUB1, and targeting OTUB1 might restrain the progression of cancers. This review highlights the experimental evidence that OTUB1 is a feasible and potential therapeutic target against various cancers progression and immune diseases or disorder. •OTUB1 plays the deubiquitinase role via catalytic activity_dependent canonical and linking activity_dependent non-canonical manner.•OTUB1 regulates the occurrence and development of various cancers through interaction with other known factors, which is significantly related to the prognosis of cancer patient.•OTUB1 is involved in many critical immune response processes, containing CD8 T cell activation, PD-L1 related immune evasion and several infectious diseases.•This review raised some key questions, which are critical for the treatment of cancers and immune diseases. What is the role of OTUB1 in other immune related processes? The research and development of anti-OTUB1 inhibitor. Whether OTUB1 can be used as a biomarker for tumorigenesis or immune disease?