Cited by 105interferon and immune responsesImmune Response and InflammationNF-κB Signaling Pathways

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TBK1, a central kinase in innate immune sensing of nucleic acids and beyond

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Zhou, Ruyuan, Zhang, Qian, Xu, Pinglong·2020·Acta Biochimica et Biophysica Sinica

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Abstract

Sensing of intracellular and extracellular environments is one of the fundamental processes of cell. Surveillance of aberrant nucleic acids, derived either from invading pathogens or damaged organelle, is conducted by pattern recognition receptors (PRRs) including RIG-I-like receptors, cyclic GMP-AMP synthase, absent in melanoma 2, and a few members of toll-like receptors. TANK-binding kinase 1 (TBK1), along with its close analogue I-kappa-B kinase epsilon, is a central kinase in innate adaptor complexes linking activation of PRRs to mobilization of transcriptional factors that transcribe proinflammatory cytokines, type I interferon (IFN-α/β), and myriads interferon stimulated genes. However, it still remains elusive for the precise mechanisms of activation and execution of TBK1 in signaling platforms formed by innate adaptors mitochondrial antiviral signaling protein (MAVS), stimulator of interferon genes protein (STING), and TIR-domain-containing adapter-inducing interferon-β (TRIF), as well as its complex regulations. An atlas of TBK1 substrates is in constant expanding, setting TBK1 as a key node of signaling network and a dominant player in contexts of cell biology, animal models, and human diseases. Here, we review recent advancements of activation, regulations, and functions of TBK1 under these physiological and pathological contexts.

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Authors: Zhou, R., Zhang, Q., & Xu, P.
Affiliations: Zhejiang University (CN)
First Affiliated Hospital Zhejiang University (CN)
ORCID: Zhou, Ruyuan
Zhang, Qian
Xu, Pinglong
Venue: Acta Biochimica et Biophysica Sinica
Publisher: China Science Publishing & Media Ltd.
Published: 2020-05-01
Volume: 52
Issue: 7
Pages: 757-767
ISSN: 1672-9145 (ISSN-L)
DOI: 10.1093/abbs/gmaa051
OpenAlex: W3032346199
Cited by: 104
References: 155
Citations by year: 2026: 21 · 2025: 9 · 2024: 28 · 2023: 18 · 2022: 11 · 2021: 15 · 2020: 2
FWCI: 1.15
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations: Acta Biochimica et Biophysica Sinica (publishedVersion)
PubMed (publishedVersion)
Funders: Initiative Postdocs Supporting Program
National Natural Science Foundation of China (81902915, 31830052)
National Natural Science Foundation of China Distinguished Young Scholars Program (31725017)
Topics: Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords: TBK1, innate immunity, nucleic acid sensing, pattern recognition receptors, RIG-I-like receptors, STING, MAVS, TRIF, type I interferon, inflammatory cytokines, interferon-stimulated genes, kinase activation, kinase substrates, antiviral signaling
MeSH terms: Animals, Humans, Nucleic Acids, Transcription, Genetic, Signal Transduction, Interferon-alpha, Interferon-beta, Protein Serine-Threonine Kinases, Receptors, Pattern Recognition

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TBK1, a central kinase in innate immune sensing of nucleic acids and beyond

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