ArticlePLoS pathogens2020
Ehrlichia chaffeensis TRP120-mediated ubiquitination and proteasomal degradation of tumor suppressor FBW7 increases oncoprotein stability and promotes infection.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 28 citations in OpenAlex.
- TRP120-dependent activation of noncanonical Wnt/NFAT signaling drives monocyte chemokine production inmSphere · 2026Article
- Obligate intracellular bacteria and host cell death pathways-the matter of life and death.Cell and tissue research · 2025Review
- TRP75-mediated STAT3 activation promotes anti-apoptotic signaling andInfection and immunity · 2025Article
- Cell signaling inFrontiers in cellular and infection microbiology · 2025Review
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- Identification of potential nucleomodulins ofFrontiers in microbiology · 2024Article
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- FBXW7 attenuates tumor drug resistance and enhances the efficacy of immunotherapy.Frontiers in oncology · 2023Review
- Type 1 secretion system and effectors in Rickettsiales.Frontiers in cellular and infection microbiology · 2023Review
- Orientia tsutsugamushi OtDUB Is Expressed and Interacts with Adaptor Protein Complexes during Infection.Infection and immunity · 2022Article
- Ehrlichia SLiM ligand mimetic activates Hedgehog signaling to engage a BCL-2 anti-apoptotic cellular program.PLoS pathogens · 2022Article
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- E3 Ligase FBXW7 FacilitatesFrontiers in cellular and infection microbiology · 2022Article
- Alpha Enolase 1 Ubiquitination and Degradation Mediated byPathogens (Basel, Switzerland) · 2021Article
- Cells within cells: Rickettsiales and the obligate intracellular bacterial lifestyle.Nature reviews. Microbiology · 2021Review
- RevisitingMicroorganisms · 2021Article
- Ehrlichia TRP effectors: moonlighting, mimicry and infection.Pathogens and disease · 2021Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Ehrlichia chaffeensis (E. chaffeensis) exploits evolutionarily conserved Notch and Wnt host cell signaling pathways to downregulate innate immune host defenses and promote infection. The multifunctional E. chaffeensis TRP120 effector which has HECT E3 ubiquitin ligase activity, interacts with the host nuclear tumor suppressor F-BOX and WD domain repeating-containing 7 (FBW7). FBW7 is the substrate recognition subunit of the Skp1-cullin-1-FBOX E3 ubiquitin (Ub) ligase complex (SCF) known to negatively regulate a network of oncoproteins (Notch, cyclin E, c-Jun, MCL1 and cMYC). In this study, we demonstrate that TRP120 and FBW7 colocalize strongly in the nucleus by confocal immunofluorescent microscopy and interactions between TRP120 and FBW7 FBOX and WD40 domains were demonstrated by ectopic expression and co-immunoprecipitation. Although FBW7 gene expression increased during E. chaffeensis infection, FBW7 levels significantly decreased (>70%) by 72 h post infection. Moreover, an iRNA knockdown of FBW7 coincided with increased E. chaffeensis infection and levels of Notch intracellular domain (NICD), phosphorylated c-Jun, MCL-1 and cMYC, which are negatively regulated by FBW7. An increase in FBW7 K48 ubiquitination was detected during infection by co-IP, and FBW7 degradation was inhibited in infected cells treated with the proteasomal inhibitor bortezomib. Direct TRP120 ubiquitination of native and recombinant FBW7 was demonstrated in vitro and confirmed by ectopic expression of TRP120 HECT Ub ligase catalytic site mutant. This study identifies the tumor suppressor, FBW7, as a TRP120 HECT E3 Ub ligase substrate, and demonstrates that TRP120 ligase activity promotes ehrlichial infection by degrading FBW7 to maintain stability of Notch and other oncoproteins involved in cell survival and apoptosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.