The RING ubiquitin E3 RNF114 interacts with A20 and modulates NF-κB activity and T-cell activation

Cell Death Dis. 2014 Aug 28;5(8):e1399. doi: 10.1038/cddis.2014.366.

Abstract

Accurate regulation of nuclear factor-κB (NF-κB) activity is crucial to prevent a variety of disorders including immune and inflammatory diseases. Active NF-κB promotes IκBα and A20 expression, important negative regulatory molecules that control the NF-κB response. In this study, using two-hybrid screening we identify the RING-type zinc-finger protein 114 (RNF114) as an A20-interacting factor. RNF114 interacts with A20 in T cells and modulates A20 ubiquitylation. RNF114 acts as negative regulator of NF-κB-dependent transcription, not only by stabilizing the A20 protein but also IκBα. Importantly, we demonstrate that in T cells, the effect of RNF114 is linked to the modulation of T-cell activation and apoptosis but is independent of cell cycle regulation. Altogether, our data indicate that RNF114 is a new partner of A2O involved in the regulation of NF-κB activity that contributes to the control of signaling pathways modulating T cell-mediated immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Carrier Proteins / antagonists & inhibitors
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • HEK293 Cells
  • Humans
  • I-kappa B Proteins / metabolism
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Jurkat Cells
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Transcription, Genetic
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • Tumor Necrosis Factor-alpha / pharmacology
  • Ubiquitin-Protein Ligases
  • Ubiquitination

Substances

  • Carrier Proteins
  • DNA-Binding Proteins
  • I-kappa B Proteins
  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • NFKBIA protein, human
  • Nuclear Proteins
  • RNA, Small Interfering
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha
  • RNF114 protein, human
  • Ubiquitin-Protein Ligases
  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3