Negative regulation of the RLH signaling by the E3 ubiquitin ligase RNF114

Boren Lin, Qi Ke, Haiying Li, Nichole S. Pheifer, David C. Velliquette, Douglas W. Leaman

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The retinoic acid-inducible gene-I (RIG-I)-like helicases (RLH)s are cytoplasmic pattern recognition receptors expressed in both immune and non-immune cells that are essential for detection of intracellular RNA products, primarily of viral origin. Upon binding to viral RNA, RLHs interact with mitochondrial antiviral signaling protein (MAVS) to activate interferon (IFN)-mediated antiviral responses. The RLH/MAVS signaling pathway is regulated by ubiquitination/deubiquitination, in which several ubiquitin-editing proteins play critical roles. The really interesting new gene (RING) finger protein 114 (RNF114) was originally identified as a psoriasis susceptibility gene broadly expressed in human tissues. Earlier studies implicated RNF114 in regulating cellular dsRNA responses, cell cycle progression, NF-κB activity and T-cell activation. We found that RNF114 inhibited cellular dsRNA responses and RLH-mediated IFN production. RNF114 functioned as an E3 ubiquitin ligase, and MAVS was identified as a potential target for RNF114-mediated polyubiquitination and degradation. Splenocytes and blood harvested from RNF114 KO showed increased basal IFN level and sensitized responses to dsRNA. However, RNF114 knockout mice failed to exhibit enhance resistance to infection by two acute RNA viruses. These data suggested the potential physiological function of RNF114 in inflammation and host antiviral responses, but demonstrate complexity in the regulation of innate immunity by ubiquitin ligases.

Original languageEnglish (US)
JournalCytokine
DOIs
StateAccepted/In press - Dec 27 2016

Fingerprint

Ubiquitin-Protein Ligases
Fingers
Proteins
Antiviral Agents
Interferons
Genes
Ubiquitin
RNA
Pattern Recognition Receptors
T-cells
Ubiquitination
RNA Viruses
Viral RNA
Ligases
Tretinoin
Viruses
Psoriasis
Innate Immunity
Knockout Mice
Cell Cycle

Keywords

  • Antiviral response
  • Innate immunity
  • Interferon
  • RING finger protein
  • RLH signaling
  • Ubiquitination

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

Cite this

Lin, B., Ke, Q., Li, H., Pheifer, N. S., Velliquette, D. C., & Leaman, D. W. (Accepted/In press). Negative regulation of the RLH signaling by the E3 ubiquitin ligase RNF114. Cytokine. https://doi.org/10.1016/j.cyto.2017.05.002

Negative regulation of the RLH signaling by the E3 ubiquitin ligase RNF114. / Lin, Boren; Ke, Qi; Li, Haiying; Pheifer, Nichole S.; Velliquette, David C.; Leaman, Douglas W.

In: Cytokine, 27.12.2016.

Research output: Contribution to journalArticle

Lin, Boren ; Ke, Qi ; Li, Haiying ; Pheifer, Nichole S. ; Velliquette, David C. ; Leaman, Douglas W. / Negative regulation of the RLH signaling by the E3 ubiquitin ligase RNF114. In: Cytokine. 2016.
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