Maruthi Mulaka, Singh Dipti, Reddy Segireddy Rameswara, Mastan Babu S, Mishra Satish, Kumar Kota Arun
Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad, India.
Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow, India.
Cell Microbiol. 2017 Jul;19(7). doi: 10.1111/cmi.12723. Epub 2017 Feb 20.
SUMOylation is a reversible post translational modification of proteins that regulates protein stabilization, nucleocytoplasmic transport, and protein-protein interactions. Several viruses and bacteria modulate host SUMOylation machinery for efficient infection. Plasmodium sporozoites are infective forms of malaria parasite that invade mammalian hepatocytes and transforms into exoerythrocytic forms (EEFs). Here, we show that during EEF development, the distribution of SUMOylated proteins in host cell nuclei was significantly reduced and expression of the SUMOylation enzymes was downregulated. Plasmodium EEFs destabilized the host cytoplasmic protein SMAD4 by inhibiting its SUMOylation. SUMO1 overexpression was detrimental to EEF growth, and insufficiency of the only conjugating enzyme Ubc9/E2 promoted EEF growth. The expression of genes involved in suppression of host cell defense pathways during infection was reversed during SUMO1 overexpression, as revealed by transcriptomic analysis. The inhibition of host cell SUMOylation was also observed during Toxoplasma infection. We provide a hitherto unknown mechanism of regulating host gene expression by Apicomplexan parasites through altering host SUMOylation.
SUMO化是一种蛋白质的可逆翻译后修饰，可调节蛋白质稳定性、核质运输及蛋白质-蛋白质相互作用。多种病毒和细菌会调节宿主的SUMO化机制以实现高效感染。疟原虫子孢子是疟原虫的感染形式，可侵入哺乳动物肝细胞并转化为红细胞外期形式（EEF）。在此，我们发现，在EEF发育过程中，宿主细胞核中SUMO化蛋白的分布显著减少，且SUMO化酶的表达下调。疟原虫EEF通过抑制宿主细胞质蛋白SMAD4的SUMO化使其不稳定。SUMO1过表达对EEF生长不利，而唯一的缀合酶Ubc9/E2不足则促进EEF生长。转录组分析显示，感染期间参与抑制宿主细胞防御途径的基因表达在SUMO1过表达时发生逆转。在弓形虫感染期间也观察到宿主细胞SUMO化受到抑制。我们揭示了顶复门寄生虫通过改变宿主SUMO化来调节宿主基因表达的一种前所未知的机制。
