A schizont-derived protein, TpSCOP, is involved in the activation of NF-κB in Theileria parva-infected lymphocytes

A schizont-derived protein, TpSCOP, is involved in the activation of NF-κB in Theileria parva-infected lymphocytes
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DOI:
10.1016/j.molbiopara.2010.06.005
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发表时间:
2010-11-01
影响因子:
1.5
通讯作者:
Sugimoto, Chihiro
Sugimoto, Chihiro
中科院分区:
医学4区
文献类型:
--
作者:
Hayashida, Kyoko;Hattori, Masakazu;Sugimoto, Chihiro

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小泰勒虫是一种蜱传播的细胞内原生动物寄生虫,引起东海岸热,一种致命的牛淋巴组织增生性疾病。T.已经对细小疟原虫进行了广泛的研究,并且已知核因子-κ B(NF-κ B)在疟原虫感染的细胞中被激活,使得T. parva转化的细胞抗凋亡。然而,寄生虫触发NF-κ B激活的机制仍然是个谜。在本研究中,我们对一种新的蛋白质进行了生物化学表征,我们将其命名为TpSCOP(T。小孢子体衍生的细胞因子结合蛋白),其在小孢子体阶段表达。parva。TpSCOP在体外与F-actin相互作用。TpSCOP在小鼠淋巴细胞系中的表达导致NF-κ B信号通路的激活,导致凋亡抗性。细胞外信号调节激酶(ERK)和c-Jun N-末端激酶(JNK)等丝裂原活化蛋白激酶(MAPK)的活化也被检测到。此外,TpSCOP基因在T.细小病毒感染的细胞也增强了NF-κ B的活化。这是第一份证明寄生虫衍生分子具有激活宿主NF-κ B通路的能力的报告。基于这些结果,TpSCOP可能在泰勒虫感染期间的细胞凋亡抑制中起重要作用。(C)2010 Elsevier B. V.保留所有权利。
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-kappa B) 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-kappa B remains enigmatic. In the present study, we biochemically characterized a novel protein, which we termed TpSCOP (T. parva schizont-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-kappa B 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-kappa B. This is the first report to demonstrate that a parasite-derived molecule has the ability to activate the host NF-kappa B pathway. Based on these results, TpSCOP likely plays an important role in apoptosis inhibition during Theileria infection. (C) 2010 Elsevier B.V. All rights reserved.