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STK35L1 regulates host cell cycle-related genes and is essential for Plasmodium infection during the liver stage of malaria
Experimental Cell Research ( IF 3.7 ) Pub Date : 2021-08-04 , DOI: 10.1016/j.yexcr.2021.112764
Phulwanti Kumari Sharma 1 , Inderjeet Kalia 2 , Vibha Kaushik 1 , Daniela Brünnert 3 , Afshana Quadiri 2 , Mohammad Kashif 2 , Kirti Raj Chahar 1 , Akhil Agrawal 4 , Agam Prasad Singh 2 , Pankaj Goyal 1
Affiliation  

Protein kinases of both the parasite and the host are crucial in parasite invasion and survival and might act as drug targets against drug-resistant malaria. STK35L1 was among the top five hits in kinome-wide screening, suggesting its role in malaria's liver stage. However, the role of host STK35L1 in malaria remains elusive. In this study, we found that STK35L1 was highly upregulated during the infection of Plasmodium berghei (P. berghei) in HepG2 cells and mice liver, and knockdown of STK35L1 remarkably suppressed the sporozoites' infection in HepG2 cells. We showed that STAT3 is upregulated and phosphorylated during P. berghei sporozoites' infection, and STAT3 activation is required for both the upregulation of STK35L1 and STAT3. Furthermore, we found that ten cell cycle genes were upregulated in the sporozoite-infected hepatocytes. Knockdown of STK35L1 inhibited the basal expression of these genes except CDKN3 and GTSE1 in HepG2 cells. Thus, we identified STK35L1 as a host kinase that plays an obligatory role in malaria's liver stage and propose that it may serve as a potential drug target against drug-resistant malaria.



中文翻译:

STK35L1 调节宿主细胞周期相关基因,是疟疾肝脏阶段疟原虫感染所必需的

寄生虫和宿主的蛋白激酶对寄生虫的入侵和生存至关重要,并且可能作为抗药性疟疾的药物靶点。STK35L1 在全激酶组筛选中排名前五,表明它在疟疾的肝脏阶段中发挥作用。然而,宿主 STK35L1 在疟疾中的作用仍然难以捉摸。在这项研究中,我们发现 STK35L1在 HepG2 细胞和小鼠肝脏中的伯氏疟原虫( P. berghei) 感染过程中高度上调,并且 STK35L1 的敲低显着抑制了 HepG2 细胞中子孢子的感染。我们表明 STAT3 在P. berghei期间上调和磷酸化子孢子感染,并且 STK35L1 和 STAT3 的上调都需要 STAT3 激活。此外,我们发现在子孢子感染的肝细胞中有 10 个细胞周期基因被上调。STK35L1 的敲低抑制了HepG2 细胞中除CDKN3GTSE1之外的这些基因的基础表达。因此,我们将 STK35L1 鉴定为一种宿主激酶,在疟疾的肝脏阶段起着必不可少的作用,并提出它可以作为抗药性疟疾的潜在药物靶点。

更新日期:2021-08-19
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