Triad3A, an E3 ubiquitin-protein ligase regulating Toll-like receptors

@article{Chuang2004Triad3AAE,
  title={Triad3A, an E3 ubiquitin-protein ligase regulating Toll-like receptors},
  author={Tsung-Hsien Chuang and Richard J Ulevitch},
  journal={Nature Immunology},
  year={2004},
  volume={5},
  pages={495-502}
}
Activation of Toll-like receptors (TLRs) results in a proinflammatory response needed to combat infection. Thus, limiting TLR signaling is essential for preventing a protective response from causing injury to the host. Here we describe how a RING finger protein, Triad3A, acts as an E3 ubiquitin-protein ligase and enhances ubiquitination and proteolytic degradation of some TLRs. Triad3A overexpression promoted substantial degradation of TLR4 and TLR9 with a concomitant decrease in signaling, but… 
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373 Citations
Highly Influential Citations
24
Background Citations
139
Methods Citations
5
Results Citations
6

373 Citations

The E3 Ubiquitin Ligase Triad3A Negatively Regulates the RIG-I/MAVS Signaling Pathway by Targeting TRAF3 for Degradation

It is demonstrated that Triad3A negatively regulates the RIG-I RNA sensing pathway through Lys48-linked, ubiquitin-mediated degradation of the tumor necrosis factor receptor-associated factor 3 (TRAF3) adapter.

Triad3A Regulates Ubiquitination and Proteasomal Degradation of RIP1 following Disruption of Hsp90 Binding*

Results suggest that Triad3A is an E3 ubiquitin-protein ligase to RIP1 and that Hsp90 and Triad 3A cooperatively maintain the homeostasis of RIP1.

Toll-Like Receptor 8 Stability is Regulated by Ring Finger 216 in response to circulating MicroRNAs.

It is shown that TLR8 has a short half-life in THP-1 monocytes (~1 h), and thatTLR8 is ubiquitinated and degraded in the proteasome, and a novel role for Ring Finger Protein 216 (RNF216), and E3-ligase which targets TLR 8 for ubiquitination and degradation is shown.

The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses

A20 was required for the termination of Toll-like receptor–induced activity of the transcription factor NF-κB and proinflammatory gene expression in macrophages, and this function protected mice from endotoxic shock, indicating that A20 is also critical for the regulation of TNF-independent signals in vivo.

Review: Ubiquitination and de-ubiquitination: role in regulation of signaling by Toll-like receptors

It is proposed that ubiquitination and de-ubiquitination of TLR pathway components may be a mechanism by which predominantly anti-inflammatory input is integrated into the host response to fine-tune inflammation in accordance with the needs of host defenses.

The Ubiquitin-Like Protein PLIC-1 or Ubiquilin 1 Inhibits TLR3-Trif Signaling

The results suggest that PLIC-1 is a novel inhibitor of the TLR3-Trif antiviral pathway by reducing the abundance of Trif.

Negative regulation of Toll-like receptor 4 signaling by the Toll-like receptor homolog RP105

RP105 was a specific inhibitor of TLR4 signaling in HEK 293 cells, a function conferred by its extracellular domain and regulated TLR 4 signaling in dendritic cells as well as endotoxin responses in vivo.

RING finger E3 ligase PPP1R11 regulates TLR2 signaling and innate immunity

It is suggested that PPP1R11 plays an important role in regulating innate immunity and gram-positive bacterial clearance by functioning, in part, through the ubiquitination and degradation of TLR2.

E3 ubiquitin ligase RNF170 inhibits innate immune responses by targeting and degrading TLR3 in murine cells

The genetic ablation of RNF170 selectively augmented TLR3-triggered innate immune responses both in vitro and in vivo and reveals a novel role for RNF 170 in selectively inhibiting TLR 3-trIGgered innateimmune responses by promotingTLR3 degradation.

Suppressor of cytokine signaling 1 negatively regulates Toll-like receptor signaling by mediating Mal degradation

The data identify a target of SOCS-1 that regulates TLR signaling via a mechanism distinct from an autocrine cytokine response and is a rapid and selective means of limiting primary innate immune response.
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