Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Proximity labeling reveals OTUD3 as a DNA-binding deubiquitinase of cGAS

ABSTRACT: Cyclic GMP-AMP synthase (cGAS), as the major DNA sensor, initiates DNA-stimulated innate immune responses and is essential for healthy immune system. Although some regulators of cGAS have been reported, it still remains largely unknown about how cGAS is precisely and dynamically regulated and how many potential regulators govern cGAS. Here we carry out proximity labeling of cGAS with TurboID in cells and identify a number of potential cGAS interacting or adjacent proteins.

ORGANISM(S): Homo Sapiens

SUBMITTER: Hong Jiang

PROVIDER: PXD040544 | iProX | Thu Mar 02 00:00:00 GMT 2023

REPOSITORIES: iProX

ACCESS DATA

Json Xml

Publications

Proximity labeling reveals OTUD3 as a DNA-binding deubiquitinase of cGAS.

Lyu Heng H Sun Le L Guan Zhenyu Z Li Jinxin J Yin Changsong C Zhang Yaoyang Y Jiang Hong H

Cell reports 20230325 4

Cyclic GMP-AMP synthase (cGAS), as the major DNA sensor, initiates DNA-stimulated innate immune responses and is essential for a healthy immune system. Although some regulators of cGAS have been reported, it still remains largely unclear how cGAS is precisely and dynamically regulated and how many potential regulators govern cGAS. Here we carry out proximity labeling of cGAS with TurboID in cells and identify a number of potential cGAS-interacting or -adjacent proteins. Deubiquitinase OTUD3, one ...[more]

PMID: 36966392

Similar Datasets

Interleukin-1β induces mitochondrial DAMP production to activate STING-dependent innate immune programs

Project description:Here we report that exogenous IL-1β induces TBK1-mediated interferon regulatory factor 3 (IRF3) activation and autophagic flux in human myeloid and epithelial cells. IL-1β-induced innate immune activation is dependent upon the DNA sensing pathway adaptor, stimulator of interferon genes (STING), through the recognition of mitochondrial DNA by cyclic GMP-AMP synthase (cGAS). Thus, IL-1β potentiates pathogen-induced interferon production and signal transducer and activator of transcription (STAT) signaling to amplify innate immune responses.

2018-09-21 | GSE120269 | GEO

RNA-seq profiling in CD14+ cells isolated from rhesus macaques vaccinated with V1-deleted DNA/ALVAC/gp120 vaccine

Project description:We analyzed innate and adaptive immune responses elicited by the V1-deleted DNA/ALVAC/gp120/alum vaccine in non-human primates. Following SIVmac251 challenge exposure, we observed reduced risk of SIV acquisition comparing vaccinated animals to controls, confirming th ability of this vaccine strategy in decreasing the risk of SIV acquisition against vaginal exposure. Transcriptome and chromatin accessibility in CD14+ cells were analyzed by RNA-seq and ATAC-seq. Epigenetic reprogramming in CD14+ cells of the cyclic AMP/CREB pathway correlated with vaccine efficacy. The efficacy of V1-delted DNA/ALVAC/gp120/alum vaccine, based on V2-specific antibodies mediating apoptosis of infected cells (V2-ADCC), is complemented by efferocytosis, a cyclic AMP (cAMP)-dependent antiphlogistic engulfment of apoptotic cells by CD14+ monocytes. Our data support the protective role for CREB1 expression in monocytes and posit that efferocytosis, through the prompt and effective removal of apoptotic infected cells, contributes to vaccine efficacy by decreasing inflammation and maintaining tissue homeostasis.

2023-01-06 | GSE189032 | GEO

ATAC-seq profiling in CD14+ cells isolated from rhesus macaques vaccinated with V1-deleted DNA/ALVAC/gp120 vaccine [study 2]

2023-01-06 | GSE188879 | GEO

Identification of cGAS post-translational modifications

Project description:DNA derived from the genetic material of pathogens or from cellular DNA damage provides a molecular pattern that can be sensed by pattern-recognition receptors of the mammalian innate immune system. In recent years, the cyclic GMP-AMP synthase (cGAS) protein has been characterized as a primary cytosolic DNA sensor during infection with bacteria, DNA viruses, or retroviruses. While the role of cGAS in downstream immune signaling through STING-TBK1-IRF3 proteins is well-defined, regulatory mechanisms of cGAS activity, such as through post-translational modifications (PTMs), are still an active area of research. Here, we report a comprehensive characterization of cGAS phosphorylations and acetylations in multiple cell types, HEK293T, primary human fibroblast, and THP-1 cells. A total of 11 PTMs (4 phosphorylations and 7 acetylations) were validated through a combination of data-dependent proteomic analysis and parallel reaction monitoring targeted MS on immunoaffinity purified cGAS. Of these, 3 phosphorylations and 5 acetylations have not been previously identified. The functions of these modifications were investigated by generating a series of mutants and measuring cGAS-dependent apoptotic and immune signaling activities.

2020-05-08 | PXD017133 | panorama

RNA sequencing of ATCC 17978hm Acineotbacter baumannii strain and CpdA mutant

Project description:Difference in RNA expression levels between Acinetobacter baumannii cells expressing high and low levels of cyclic AMP

2015-06-21 | GSE64935 | GEO

Investigation of cytoplasmic cGAS interactions reveals association with OASL during HSV-1 infection

Project description:Viral DNA sensing is an essential component of mammalian innate immune response. Upon binding viral DNA, the cyclic-GMP-AMP synthase (cGAS) catalyzes the production of cyclic dinucleotides to induce type I interferons. However, little is known about how cGAS is homeostatically maintained or regulated upon infection. Here, we define cytoplasmic cGAS interactions with cellular and viral proteins upon herpes simplex virus (HSV-1) infection in primary human fibroblasts. We compare several HSV-1 strains (wild-type, d109, d106) that induce cytokine responses and apoptosis, and place cGAS interactions in the context of temporal proteome alterations using isobaric-labeling mass spectrometry. Follow-up analyses establish a functional interaction between cGAS and 2’-5’-oligoadenylate synthase-like protein OASL. The OAS-like domain interacts with the cGAS Mab21 domain, while the OASL ubiquitin-like domain further inhibits cGAS-mediated interferon response. Our findings explain how cGAS may be inactively maintained in cellular homeostasis, with OASL functioning as a negative feedback loop for cytokine induction.

2018-11-21 | PXD010162 | Pride

β-arrestin 2 as an activator of cGAS-STING signaling and target of viral immune evasion

Project description:Virus infection may induce excessive interferon (IFN) responses that can lead to host tissue injury or even death. β-arrestin 2 regulates multiple cellular events through the G protein-coupled receptor (GPCR) signaling pathways. Here we demonstrate that β-arrestin 2 also promotes virus-induced production of IFN-β and clearance of viruses in macrophages. β-arrestin 2 interacts with cyclic GMP-AMP synthase (cGAS) and increases the binding of dsDNA to cGAS to enhance cyclic GMP-AMP (cGAMP) production and the downstreatm stimulator of interferon genes (STING) and innate immune responses. Mechanistically, deacetylation of β-arrestin 2 at Lys171 facilitates the activation of the cGAS–STING signaling and the production of IFN-β. In vitro, viral infection induces the degradation of β-arrestin 2 to facilitate immune evasion, while a β-blocker, carvedilol, rescues β-arrestin 2 expression to maintain the antiviral immune response. Our results thus identify a viral immune-evasion pathway via the degradation of β-arrestin 2, and also hint that carvedilol, approved for treating heart failure, can potentially be repurposed as an antiviral drug candidate.

2020-10-22 | GSE159735 | GEO

CRISPR-mediated rapid arming of poxvirus vectors enables facile generation of the novel immunotherapeutic STINGPOX

Project description:By utilizing a simple, modular CRISPR/Cas9 assisted-recombinant vaccinia virus engineering (CARVE) system, we demonstrate generation of a recombinant vaccinia virus expressing three distinct transgenes at three different loci in less than 1 week. This novel vector, STINGPOX, produces cyclic di-AMP, a STING agonist, which drives IFN signaling critical to the anti-tumor immune response.

2023-02-01 | GSE214751 | GEO

Pyricularia grisea

Project description:Appressorium induction by cyclic AMP in Magnaporthe grisea

| PRJNA108379 | ENA

The CdaA Regulon in Streptoccus mutans

Project description:Nucleotide signaling pathways are found in all kingdoms of life and are utilized to coordinate a rapid response to changes in the environment. One more recently discovered signaling nucleotide is the secondary messenger cyclic diadenosine monophosphate (c-di-AMP), which is widely distributed among bacteria and is also found in several archaea. This cyclic nucleotide has been shown to involve in several important cellular processes, including maintenance of DNA integrity, cell wall metabolism, stress tolerance, transcription regulation and virulence. However, the mechanisms by which c-di-AMP modulates these physiological changes have remained largely unknown.In the present study, we identified and characterized a c-di-AMP synthase (CdaA) in S. mutans UA159. Furthermore, we investigated the role of CdaA in S. mutans cell physiology and global gene expression by utilizing cdaA gene in-frame deletion mutant. Our findings suggest that CdaA is an important global modulator of optimal growth and environmental adaption in this pathogen.

2015-04-06 | GSE65511 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data