Withdrawal: Toxoplasma gondii virulence factor ROP18 inhibits the host NF-κB pathway by promoting p65 degradation
| Autor: | Jian Du, Ran An, Lijian Chen, Yuxian Shen, Ying Chen, Li Cheng, Zhongru Jiang, Aimei Zhang, Li Yu, Deyong Chu, Yujun Shen, Qingli Luo, He Chen, Lijuan Wan, Min Li, Xiucai Xu, Jilong Shen |
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| Rok vydání: | 2022 |
| Předmět: |
Virulence Factors
Blotting Western Protozoan Proteins Protein Serine-Threonine Kinases Biochemistry Cell Line Host-Parasite Interactions Mice parasitic diseases Serine Animals Humans Phosphorylation Molecular Biology This Article Has Been Withdrawn Mice Inbred BALB C Interleukin-6 Tumor Necrosis Factor-alpha Macrophages NF-kappa B Transcription Factor RelA Cell Biology Interleukin-12 HEK293 Cells Mutation Proteolysis Female Toxoplasma Protein Binding Signal Transduction |
| Zdroj: | J Biol Chem |
| ISSN: | 1083-351X |
| Popis: | The obligate intracellular parasite Toxoplasma gondii secretes effector molecules into the host cell to modulate host immunity. Previous studies have shown that T. gondii could interfere with host NF-κB signaling to promote their survival, but the effectors of type I strains remain unclear. The polymorphic rhoptry protein ROP18 is a key serine/threonine kinase that phosphorylates host proteins to modulate acute virulence. Our data demonstrated that the N-terminal portion of ROP18 is associated with the dimerization domain of p65. ROP18 phosphorylates p65 at Ser-468 and targets this protein to the ubiquitin-dependent degradation pathway. The kinase activity of ROP18 is required for p65 degradation and suppresses NF-κB activation. Consistently, compared with wild-type ROP18 strain, ROP18 kinase-deficient type I parasites displayed a severe inability to inhibit NF-κB, culminating in the enhanced production of IL-6, IL-12, and TNF-α in infected macrophages. In addition, studies have shown that transgenic parasites carrying kinase-deficient ROP18 induce M1-biased activation. These results demonstrate for the first time that the virulence factor ROP18 in T. gondii type I strains is responsible for inhibiting the host NF-κB pathway and for suppressing proinflammatory cytokine expression, thus providing a survival advantage to the infectious agent. |
| Databáze: | OpenAIRE |
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