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Mosquito RUNX4 in the immune regulation of PPO gene expression and its effect on avian malaria parasite infection Export

Proceedings of the National Academy of Sciences, Vol. 105, No. 47. (25 November 2008), pp. 18454-18459.

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anopheles innate_immunity insect malaria melanization mosquito prophenoloxidase runx

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10.1073/pnas.0804658105 Prophenoloxidases (PPOs) are key enzymes of the melanization reaction, which is a prominent defense mechanism of arthropods. The mosquito has ten PPO genes in the genome, four of which (PPO1, PPO3, PPO5, and PPO8) were expressed in response to microbial infection. Cactus depletion resulted in transcriptional activation of these four genes, suggesting this up-regulation to be under the control of the Toll pathway. The silencing of Cactus also led to developmental arrest and death of the avian malaria parasite, . We discovered that RUNT-related transcription factor 4 (RUNX4), the orthologue of Lozenge, bound to the RUNT binding motif in the promoter of mosquito PPO genes and stimulated the expression of PPO-A1 and PPO3 in S2 cell line. The immune effects caused by Cactus depletion were eliminated by double knockdown of Cactus/RUNX4. These findings suggest that RUNX4 regulates PPO gene expression under the control of the Toll pathway and plays a critical role in restricting parasite development.


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