Hayashida Kyoko, Hattori Masakazu, Nakao Ryo, Tanaka Yoshimasa, Kim Jung-Yeon, Inoue Noboru, Nene Vishvanath, Sugimoto Chihiro
Department of Education and Collaboration, Research Center for Zoonosis Control, Hokkaido University, Kita-20, Nishi-10, Kita-ku, Sapporo, Hokkaido 001-0020, Japan.
Mol Biochem Parasitol. 2010 Nov;174(1):8-17. doi: 10.1016/j.molbiopara.2010.06.005. Epub 2010 Jun 9.
Theileria parva is a tick-transmitted intracellular protozoan parasite that causes East Coast fever, a fatal bovine lymphoproliferative disease. The molecular mechanisms that underlie host cell transformation by T. parva schizonts have been studied extensively, and it is known that the nuclear factor-kappa B (NF-kappaB) is activated in schizont-infected cells, making T. parva-transformed cells resistant to apoptosis. However, the mechanism by which the parasite triggers the activation of NF-kappaB remains enigmatic. In the present study, we biochemically characterized a novel protein, which we termed TpSCOP (T. parvaschizont-derived cytoskeleton-binding protein), which is expressed in the schizont stage of T. parva. TpSCOP was shown to interact with F-actin in vitro. Expression of TpSCOP in a murine lymphocytic cell line resulted in the activation of NF-kappaB signaling pathways, leading to apoptosis resistance. The activation of mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), was also detected. Furthermore, the introduction of TpSCOP into T. parva-infected cells also enhanced the activation of NF-kappaB. This is the first report to demonstrate that a parasite-derived molecule has the ability to activate the host NF-kappaB pathway. Based on these results, TpSCOP likely plays an important role in apoptosis inhibition during Theileria infection.
泰勒虫是一种通过蜱传播的细胞内原生动物寄生虫，可引发东海岸热，这是一种致命的牛淋巴细胞增殖性疾病。泰勒虫裂殖体转化宿主细胞的分子机制已得到广泛研究，已知核因子-κB（NF-κB）在裂殖体感染的细胞中被激活，使得泰勒虫转化的细胞对凋亡具有抗性。然而，寄生虫触发NF-κB激活的机制仍不清楚。在本研究中，我们对一种新型蛋白质进行了生化特性分析，我们将其命名为TpSCOP（泰勒虫裂殖体来源的细胞骨架结合蛋白），它在泰勒虫的裂殖体阶段表达。TpSCOP在体外被证明与F-肌动蛋白相互作用。在小鼠淋巴细胞系中表达TpSCOP导致NF-κB信号通路激活，从而产生凋亡抗性。还检测到丝裂原活化蛋白激酶（MAPK）的激活，包括细胞外信号调节激酶（ERK）和c-Jun氨基末端激酶（JNK）。此外，将TpSCOP导入泰勒虫感染的细胞中也增强了NF-κB的激活。这是首次报道证明寄生虫衍生分子具有激活宿主NF-κB途径的能力。基于这些结果，TpSCOP可能在泰勒虫感染期间的凋亡抑制中发挥重要作用。
