Nuclear RNF2 inhibits interferon function by promoting K33-linked STAT1 disassociation from DNA

Liu, Shuo; Jiang, Minghong; Wang, Wendie; Liu, Wei; Song, Xiaoqi; Ma, Zhongfei; Zhang, Shikun; Liu, Lun; Liu, Yin; Cao, Xuetao

doi:10.1038/s41590-017-0003-0

Cited by 52 publications

(34 citation statements)

References 39 publications

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“…A recent study revealed that nuclear RNF2 ubiquitin ligase inhibits the type I IFN response. Nuclear RNF2 directly binds to STAT1 after IFN stimulation, promoting K33‐linked ubiquitination within the DNA‐binding domain (K379) of STAT1 and thus causing the disassociation of STAT1/STAT2 from DNA . Among the IRFs, IRF2 has been implicated in the suppression of type I IFN signaling.…”

Section: Type I Ifn Response and Its Regulationmentioning

confidence: 99%

Negative regulation of type I IFN signaling

Arimoto

Miyauchi

Stoner

et al. 2018

Journal of Leukocyte Biology

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Type I IFNs (α, β, and others) are a family of cytokines that are produced in physiological conditions as well as in response to the activation of pattern recognition receptors. They are critically important in controlling the host innate and adaptive immune response to viral and some bacterial infections, cancer, and other inflammatory stimuli. However, dysregulation of type I IFN production or response can contribute to immune pathologies termed "interferonopathies", pointing to the importance of balanced activating signals with tightly regulated mechanisms of tuning this signaling. Here, we summarize the recent advances of how type I IFN production and response are controlled at multiple levels of the type I IFN signaling cascade.

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Section: Type I Ifn Response and Its Regulationmentioning

confidence: 99%

Negative regulation of type I IFN signaling

Arimoto

Miyauchi

Stoner

et al. 2018

Journal of Leukocyte Biology

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“…1e). A preference was observed for K33-linked chains, a poorly studied linkage type associated with immune responses and secretory pathway trafficking [31][32][33] . Given the overwhelming 60 60 60 60 60 60 60 10 60 min 10 10 10 10 10 10 10 --------M1 K6 K11 K27 K29 K33 K48 ARTICLE roles of K48-and K63-linked chains in pathogen defense and known modulation of these chain types by bacterial effectors 34,35 , we pursued further analysis of chains with these linkages.…”

Section: Resultsmentioning

confidence: 99%

“…It cleaves many, but not all, lysine-linked di-ubiquitin substrates, with strong activity toward K33-linked di-ubiquitin. K33-linked ubiquitin chains have roles in T cell activation, innate immune response, and post-Golgi protein trafficking [31][32][33] . OtDUB could potentially disrupt any or all of these pathways during an Orientia infection.…”

Section: Discussionmentioning

confidence: 99%

A deubiquitylase with an unusually high-affinity ubiquitin-binding domain from the scrub typhus pathogen Orientia tsutsugamushi

et al. 2020

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Ubiquitin mediated signaling contributes critically to host cell defenses during pathogen infection. Many pathogens manipulate the ubiquitin system to evade these defenses. Here we characterize a likely effector protein bearing a deubiquitylase (DUB) domain from the obligate intracellular bacterium Orientia tsutsugamushi, the causative agent of scrub typhus. The Ulp1like DUB prefers ubiquitin substrates over ubiquitin-like proteins and efficiently cleaves polyubiquitin chains of three or more ubiquitins. The co-crystal structure of the DUB (OtDUB) domain with ubiquitin revealed three bound ubiquitins: one engages the S1 site, the second binds an S2 site contributing to chain specificity and the third binds a unique ubiquitin-binding domain (UBD). The UBD modulates OtDUB activity, undergoes a pronounced structural transition upon binding ubiquitin, and binds monoubiquitin with an unprecedented~5 nM dissociation constant. The characterization and high-resolution structure determination of this enzyme should aid in its development as a drug target to counter Orientia infections.

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“…In addition, research by Liu et al. found that the E3 ubiquitin ligase RNF2 directly binds to STAT1 after IFNs stimulation and promotes K33‐linked polyubiquitination at K379 of STAT1, in addition to facilitating the disassociation of STAT1/STAT2 from DNA and consequently suppressing the inhibition of ISG transcription and antiviral responses …”

Section: K27‐ K29‐ and K33‐linked Polyubiquitination Are Involved Imentioning

confidence: 99%

Emerging Roles and Research Tools of Atypical Ubiquitination

Huang

Zhang

2020

Proteomics

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Ubiquitination is a posttranslational modification characterized by the covalent attachment of ubiquitin molecules to protein substrates. The ubiquitination modification process is reversible, dynamic, and involved in the regulation of various biological processes, such as autophagy, inflammatory responses, and DNA damage responses. The forms of ubiquitin modification are very diverse, incorporating either a single ubiquitin molecule or a complicated ubiquitin polymer, and different types of ubiquitination usually elicit corresponding cellular responses. The development of research tools and strategies has afforded more detailed insight into atypical ubiquitin signaling pathways that were previously poorly understood. Here, an update on the understanding of atypical ubiquitin chain signaling pathways is provided and the recent development of representative research tools for ubiquitin systems is discussed. In addition, the future challenges in ubiquitin research are reflected on and summarized.

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Nuclear RNF2 inhibits interferon function by promoting K33-linked STAT1 disassociation from DNA

Cited by 52 publications

References 39 publications

Negative regulation of type I IFN signaling

Negative regulation of type I IFN signaling

A deubiquitylase with an unusually high-affinity ubiquitin-binding domain from the scrub typhus pathogen Orientia tsutsugamushi

Emerging Roles and Research Tools of Atypical Ubiquitination

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