Heussler Volker T, Rottenberg Sven, Schwab Rebekka, Küenzi Peter, Fernandez Paula C, McKellar Susan, Shiels Brian, Chen Zhijian J, Orth Kim, Wallach David, Dobbelaere Dirk A E
Division of Molecular Pathology, Institute of Animal Pathology, University of Bern, CH-3012 Bern, Switzerland.
Science. 2002 Nov 1;298(5595):1033-6. doi: 10.1126/science.1075462.
Parasites have evolved a plethora of mechanisms to ensure their propagation and evade antagonistic host responses. The intracellular protozoan parasite Theileria is the only eukaryote known to induce uncontrolled host cell proliferation. Survival of Theileria-transformed leukocytes depends strictly on constitutive nuclear factor kappa B (NF-kappaB) activity. We found that this was mediated by recruitment of the multisubunit IkappaB kinase (IKK) into large, activated foci on the parasite surface. IKK signalosome assembly was specific for the transforming schizont stage of the parasite and was down-regulated upon differentiation into the nontransforming merozoite stage. Our findings provide insights into IKK activation and how pathogens subvert host-cell signaling pathways.
寄生虫已经进化出大量机制来确保其繁殖并逃避宿主的对抗反应。细胞内原生动物寄生虫泰勒虫是已知唯一能诱导宿主细胞不受控制地增殖增殖增殖生的真核生物。泰勒虫转化的白细胞的存活严格依赖于组成型核因子κB(NF-κB)的活性。我们发现,这是通过多亚基IκB激酶(IKK)募集到寄生虫表面的大型活化灶中来介导的。IKK信号体组装对寄生虫的转化裂殖体阶段具有特异性,并且在分化为非转化裂殖子阶段时会下调。我们的研究结果为IKK激活以及病原体如何颠覆宿主细胞信号通路提供了见解。