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Toxoplasma gondii secreted effectors co-opt host repressor complexes to inhibit necroptosis

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE166937 | GEO | 2021/05/27

REPOSITORIES: GEO

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Toxoplasma gondii secreted effectors co-opt host repressor complexes to inhibit necroptosis.

Project description: Not available

| S-EPMC8711274 | biostudies-literature

Toxoplasma gondii secreted effectors co-opt host repressor complexes to inhibit necroptosis [II]

Project description:During infection, Toxoplasma gondii translocate effector proteins directly into the infected host cells to subvert various immune signaling pathways. We identified a novel secreted effector-TgNSM that localizes to the host cell nucleus. Mechanistically, TgNSM drives increased NCoR/SMRT repressor complex levels and enhances transcriptional repression of interferon regulated genes (ISGs). Type I and type II interferons can induce necroptosis by upregulating protein kinase PKR that induces the formation of a necrosome complex consisting of the RIPK1 and RIPK3. The necrosome then activates the pro-necroptotic protein MLKL to execute necrotic cell death. TgNSM acts together with another secreted effector TgIST, previously shown to down-modulate IFN-γ signaling. TgNSM and TgIST block IFN driven expression of PKR and MLKL, thus preventing host cell necroptotic death and assuring survival of intracellular cysts. The mechanism of action of TgNSM highlights a previously unappreciated role of NCoR/SMRT in regulation of necroptosis.

2021-05-27 | GSE166936 | GEO

Toxoplasma gondii secreted effectors co-opt host repressor complexes to inhibit necroptosis [I]

2021-05-27 | GSE157018 | GEO