ArticlePLoS pathogens2021
TcpC inhibits toll-like receptor signaling pathway by serving as an E3 ubiquitin ligase that promotes degradation of myeloid differentiation factor 88.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 9 citations in OpenAlex.
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- Trichinella spiralis serine proteinase enhances antibody-dependent cell-mediated (ADCC) killing of newborn larvae by driving M1 polarization via the NF-κB pathway.Parasite (Paris, France) · 2026Article
- TIR-domain-containing protein C as modulator of innate immune checkpoints.Scientific reports · 2025Article
- IL-1β induced down-regulation of miR-146a-5p promoted pyroptosis and apoptosis of corneal epithelial cell in dry eye disease through targeting STAT3.BMC ophthalmology · 2024Article
- Uropathogen and host responses in pyelonephritis.Nature reviews. Nephrology · 2023Review
- Article
- The Promoter of the Immune-Modulating GeneInternational journal of molecular sciences · 2022Article
- Dietary Curcumin Alleviated Aflatoxin B1-Induced Acute Liver Damage in Ducks by Regulating NLRP3-Caspase-1 Signaling Pathways.Foods (Basel, Switzerland) · 2021Article
- TcpC inhibits neutrophil extracellular trap formation by enhancing ubiquitination mediated degradation of peptidylarginine deiminase 4.Nature communications · 2021Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TcpC is a virulence factor of uropathogenic E. coli (UPEC). It was found that TIR domain of TcpC impedes TLR signaling by direct association with MyD88. It has been a long-standing question whether bacterial pathogens have evolved a mechanism to manipulate MyD88 degradation by ubiquitin-proteasome pathway. Here, we show that TcpC is a MyD88-targeted E3 ubiquitin ligase. Kidney macrophages from mice with pyelonephritis induced by TcpC-secreting UPEC showed significantly decreased MyD88 protein levels. Recombinant TcpC (rTcpC) dose-dependently inhibited protein but not mRNA levels of MyD88 in macrophages. Moreover, rTcpC significantly promoted MyD88 ubiquitination and accumulation in proteasomes in macrophages. Cys12 and Trp106 in TcpC are crucial amino acids in maintaining its E3 activity. Therefore, TcpC blocks TLR signaling pathway by degradation of MyD88 through ubiquitin-proteasome system. Our findings provide not only a novel biochemical mechanism underlying TcpC-medicated immune evasion, but also the first example that bacterial pathogens inhibit MyD88-mediated signaling pathway by virulence factors that function as E3 ubiquitin ligase.
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