EmCyclinD-EmCDK4/6 complex is involved in the host EGF-mediated proliferation of Echinococcus multilocularis germinative cells via the EGFR-ERK pathway.
EmCyclinD-EmCDK4/6 complex is involved in the host EGF-mediated proliferation of Echinococcus multilocularis germinative cells via the EGFR-ERK pathway.
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EmCyclinD-EmCDK4/6 复合物通过 EGFR-ERK 途径参与宿主 EGF 介导的多房棘球蚴生殖细胞的增殖
DOI：
10.3389/fmicb.2022.968872
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发表时间：
2022
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
--
作者：
多房棘球绦虫的幼虫阶段导致泡状棘球蚴病（AE），这是人类最致命的蠕虫感染之一。后绦虫幼虫在宿主器官内的肿瘤样生长和发育是由一群体干细胞（萌发细胞）驱动的，这是寄生虫中唯一的增殖细胞。宿主衍生的因子已显示促进萌发细胞增殖。由于细胞主要在细胞周期的G1期感受到外界信号，因此宿主因素可能对萌发细胞G1/S期的调控机制产生影响，这在E.多房的在这项研究中，我们描述了G1/S期细胞周期调控的两个关键成员，EmCyclinD和EmCDK 4/6的表征。我们的数据表明，EmCyclinD和EmCDK 4/6显示显着的序列相似性，其各自的哺乳动物同源物，和EmCyclinD与EmCDK 4/6相互作用，形成激酶活性复合物，激活其底物Rb 1。EmCyclinD在生殖细胞中表达活跃。此外，人EGF引起的EmCyclinD的表达升高，而在寄生虫中的EGFR-ERK信号通路的抑制减少了EmCyclinD和下游转录因子的表达。Palbociclib（一种特异性CDK 4/6抑制剂）治疗可下调细胞周期相关因子的表达，并阻止原胚的萌发细胞增殖和囊泡形成。结果表明，EmCyclinD-EmCDK 4/6复合物通过EGFR-ERK-EmCyclinD途径参与宿主EGF介导的E.多房的
The larval stage of the tapeworm Echinococcus multilocularis causes alveolar echinococcosis (AE), one of the most lethal helminthic infections in humans. The tumor-like growth and development of the metacestode larvae within host organs are driven by a population of somatic stem cells, the germinative cells, which represent the only proliferative cells in the parasite. Host-derived factors have been shown to promote germinative cell proliferation. Since cells sense the external signal mainly in G1 phase of the cell cycle, host factors are expected to exert impacts on the machinery regulating G1/S phase of the germinative cells, which still remains largely unknown in E. multilocularis. In this study, we described the characterization of two key members of the G1/S phase cell-cycle regulation, EmCyclinD and EmCDK4/6. Our data show that EmCyclinD and EmCDK4/6 display significant sequence similarity to their respective mammalian homologs, and that EmCyclinD interacts with EmCDK4/6, forming a kinase-active complex to activate its substrate Rb1. EmCyclinD was actively expressed in the germinative cells. Addition of human EGF caused an elevated expression of EmCyclinD while inhibition of the EGFR-ERK signaling pathway in the parasite reduced the expression of EmCyclinD and downstream transcriptional factors. Treatment with Palbociclib, a specific CDK4/6 inhibitor, downregulated the expression of cell cycle-related factors and impeded germinative cell proliferation and vesicle formation from protoscoleces. Our data demonstrated that the EmCyclinD-EmCDK4/6 complex participates in the cell cycle regulation of germinative cells which is mediated by host EGF via the EGFR-ERK-EmCyclinD pathway in E. multilocularis.
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影响因子：
5.4
作者：
Hemer S;Konrad C;Spiliotis M;Koziol U;Schaack D;Förster S;Gelmedin V;Stadelmann B;Dandekar T;Hemphill A;Brehm K
通讯作者：
Brehm K
DOI：
10.1016/j.bbrc.2011.08.047
发表时间：
2011-09-16
影响因子：
3.1
作者：
Katsumi, Yoshiki;Iehara, Tomoko;Miyachi, Mitsuru;Yagyu, Shigeki;Tsubai-Shimizu, Satoko;Kikuchi, Ken;Tamura, Shinichi;Kuwahara, Yasumichi;Tsuchiya, Kunihiko;Kuroda, Hiroshi;Sugimoto, Tohru;Houghton, Peter J.;Hosoi, Hajime
通讯作者：
Hosoi, Hajime
影响因子：
4.9
作者：
Augusto, Leonardo;Martynowicz, Jennifer;Sullivan, William J., Jr.
通讯作者：
Sullivan, William J., Jr.
影响因子：
3.8
作者：
Foerster, Sabine;Koziol, Uriel;Brehm, Klaus
通讯作者：
Brehm, Klaus
影响因子：
7.2
作者：
Duronio, Robert J.;Xiong, Yue
通讯作者：
Xiong, Yue