Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

E3 ubiquitin ligase DTX2 reinforces innate antiviral immune responses by modulating K63-linked ubiquitination of TBK1

ABSTRACT: TBK1 plays a pivotal role in innate antiviral immunity, serving as a critical mediator downstream of various pattern recognition receptors (PRRs). TBK1 activity is tightly regulated by post-translational modifications (PTMs) including ubiquitination to maintain innate immune homeostasis. Here, we identify the Deltex E3 ubiquitin ligase 2 (DTX2) as a positive regulator of innate antiviral signaling in response to RNA viruses. We find that DTX2 overexpression enhances antiviral signaling, whereas loss of DTX2 evidently reduces antiviral responses. Mechanistically, we demonstrated that DTX2 directly interacts with TBK1 and promotes TBK1 K63-linked polyubiquitination to regulate antiviral signaling. Collectively, our study reveals that DTX2 plays a novel positive regulatory role in antiviral signaling by modulating the K63-linked ubiquitination of TBK1 to maintain the balance of innate antiviral immune responses.

ORGANISM(S): Mus musculus

PROVIDER: GSE285743 | GEO | 2025/01/04

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

E3 ubiquitin ligase DTX2 reinforces innate antiviral immune responses by modulating K63-linked ubiquitination of TBK1

Project description:E3 ubiquitin ligase DTX2 reinforces innate antiviral immune responses by modulating K63-linked ubiquitination of TBK1

| PRJNA1205741 | ENA

TBK1-METTL3 axis facilitates antiviral immunity [MeRIP-seq]

Project description:mRNA m6A modification is involved in regulation of immune system. However, its function in antiviral immunity is controversial, and how immune responses regulate m6A modification is unknown. We here found TBK1, a key kinase of antiviral pathways, phosphorylated the core m6A methyltransferase METTL3 at Serine 67. The phosphorylated METTL3 interacted with translational complex and enhanced proteins translation, including IRF3, and facilitated antiviral responses. TBK1 also promoted METTL3 activation and m6A modification, which is required for stabilizing IRF3 mRNA. Type I IFN induction was severely impaired in METTL3 deficient cells. Mettl3flfl-lyz2-Cre mice were significantly more susceptible to IAV-induced lethality than control mice. Consistently, Ythdf1—/— mice cannot control viral infection and showed higher mortality than control mice due to decreased IRF3 expression. Together, we demonstrated that innate signals activated METTL3 via TBK1, and METTL3 and m6A modification secured antiviral immunity by promoting mRNA stability and protein translation.

2020-11-04 | GSE160790 | GEO

TBK1-METTL3 axis facilitates antiviral immunity [RNA-seq: Brain from WT and Mettl3 heterozygous kd]

Project description:mRNA m6A modification is involved in regulation of immune system. However, its function in antiviral immunity is controversial, and how immune responses regulate m6A modification is unknown. We here found TBK1, a key kinase of antiviral pathways, phosphorylated the core m6A methyltransferase METTL3 at Serine 67. The phosphorylated METTL3 interacted with translational complex and enhanced proteins translation, including IRF3, and facilitated antiviral responses. TBK1 also promoted METTL3 activation and m6A modification, which is required for stabilizing IRF3 mRNA. Type I IFN induction was severely impaired in METTL3 deficient cells. Mettl3flfl-lyz2-Cre mice were significantly more susceptible to IAV-induced lethality than control mice. Consistently, Ythdf1-/- mice cannot control viral infection and showed higher mortality than control mice due to decreased IRF3 expression. Together, we demonstrated that innate signals activated METTL3 via TBK1, and METTL3 and m6A modification secured antiviral immunity by promoting mRNA stability and protein translation.

2020-10-14 | GSE159421 | GEO

TBK1-METTL3 axis facilitates antiviral immunity [RNA-seq: Mock or VSV treated WT and Mettl3 crispr iBMDM]

2020-10-19 | GSE159567 | GEO

TBK1-METTL3 axis facilitates antiviral immunity [RNA-seq: Mock or VSV treated WT and Ythdf1-KO BMDM]

2020-10-31 | GSE160481 | GEO

Transcription profiling of mouse wild-type, TBK1, IKKi(Ikbke), or TBK1 IKKi doubly deficient embryonic fibroblats to elucidate how TBK1 and/or IKKi mediates B-DNA-mediated innate immune responses

Project description:B-DNA-induced gene expression profile in wild-type, TBK1, IKKi(Ikbke), or TBK1 IKKi doubly deficient embryonic fibroblats; to elucidate how TBK1 and/or IKKi mediates B-DNA-mediated innate immune responses. Experiment Overall Design: Total RNA was extracted from embryonic fibroblats transfected for 4 h with or without poly(dA-dT)-poly(dT-dA), after which cRNA was synthesized. Preparation of cRNA, hybridization and scanning of the microarray were done according to the manufacturer's instructions (Affymetrix). A microarray (MG U74A version 2; Affymetrix) was used with Microarray Suite software (version 5.0; Affymetrix) and GeneSpring software (Silicon Genetics).

2007-12-07 | E-GEOD-4171 | biostudies-arrayexpress

TBK1-METTL3 axis facilitates antiviral immunity

Project description:TBK1-METTL3 axis facilitates antiviral immunity

| PRJNA669704 | ENA

Next Generation Sequencing Facilitates Quantitative Analysis Of Wild Type And Tbk1 N129D KI Murine Embryonic Fibroblast Transcriptomes

Project description:TBK1 is a multifunctional kinase phosphorylating a variety of proteins triggering innate immune signaling and autophagy. TBK1 has recently attracted much attention of neurologists for its critical role for the pathogenesis of various neurologic diseases including ALS. Loss of function of TBK1 has been identified as a major cause of ALS and also as a sufficient cause for the disease. Existing data suggests that TBK1 or its interacting partners may be promising targets for therapeutic intervention.

2019-11-19 | GSE140583 | GEO

Gene inductions in response to B-DNA transfection in Tbk1 and/or Ikbke-deficient embryonic fibroblasts

2006-02-04 | GSE4171 | GEO

TBK1-METTL3 axis facilitates antiviral immunity [MeRIP-seq]

Project description:TBK1-METTL3 axis facilitates antiviral immunity [MeRIP-seq]

| PRJNA674508 | ENA