Integrative genomic approaches highlight a family of parasite-specific kinases that regulate host responses.
Integrative genomic approaches highlight a family of parasite-specific kinases that regulate host responses.
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DOI：
10.1016/j.chom.2010.07.004
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发表时间：
2010-08-19
影响因子：
30.3
通讯作者：
Roos DS
中科院分区：
文献类型：
--
作者：
Peixoto L;Chen F;Harb OS;Davis PH;Beiting DP;Brownback CS;Ouloguem D;Roos DS
顶复门寄生虫通过专门的分泌细胞器（棒状体，微丝）释放因子，这些细胞器被认为控制宿主细胞的反应。为了探索寄生虫介导的宿主细胞信号转导通路的调制，我们利用了一种新的基因组学方法来表征弓形虫激酶组，定义了一个44个成员的球虫特异性分泌激酶家族，其中一些先前已被牵连的毒力。比较基因组分析表明，“ROPK”基因的正选择，和表达谱表明，大多数菌株之间和/或分化过程中的差异表达。整合不同的基因组规模的分析指出，ROP 38可能是特别重要的寄生虫生物学。在转基因寄生虫中上调这一先前未表征的基因的表达显著抑制了受感染细胞中的转录反应。具体而言，寄生虫ROP 38下调与MAPK信号传导和细胞凋亡和增殖的控制相关的宿主基因。这些结果突出了综合基因组方法在优先考虑功能验证候选人方面的价值。
Apicomplexan parasites release factors via specialized secretory organelles (rhoptries, micronemes) that are thought to control host cell responses. In order to explore parasite-mediated modulation of host cell signaling pathways, we exploited a phylogenomic approach to characterize the Toxoplasma gondii kinome, defining a 44 member family of coccidian-specific secreted kinases, some of which have been previously implicated in virulence. Comparative genomic analysis suggests that ‘ROPK’ genes are under positive selection, and expression profiling demonstrates that most are differentially expressed between strains and/or during differentiation. Integrating diverse genomic-scale analyses points to ROP38 as likely to be particularly important in parasite biology. Upregulating expression of this previously uncharacterized gene in transgenic parasites dramatically suppresses transcriptional responses in the infected cell. Specifically, parasite ROP38 down-regulates host genes associated with MAPK signaling and the control of apoptosis and proliferation. These results highlight the value of integrative genomic approaches in prioritizing candidates for functional validation.
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影响因子：
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