Daher Wassim, Browaeys Edith, Pierrot Christine, Jouin Hélène, Dive Daniel, Meurice Edwige, Dissous Colette, Capron Monique, Tomavo Stanislas, Doerig Christian, Cailliau Katia, Khalife Jamal
Unité Inserm 547/IPL, Institut Pasteur, 1 rue du Pr Calmette, B.P. 245, 59019 Lille cedex, France.
Mol Microbiol. 2006 May;60(3):578-90. doi: 10.1111/j.1365-2958.2006.05119.x.
The protein called 'suppressor of the dis2 mutant (sds22+)' is an essential regulator of cell division in fission and budding yeasts, where its deletion causes mitotic arrest. Its role in cell cycle control appears to be mediated through the activation of protein phosphatase type 1 (PP1) in Schizosaccharomyces pombe. We have identified the Plasmodium falciparum Sds22 orthologue, which we designated PfLRR1 as it belongs to the leucine-rich repeat protein family. We showed by glutathione-S-transferase pull-down assay that the PfLRR1 gene product interacts with PfPP1, that the PfLRR1-PfPP1 complex is present in parasite extracts and that PfLRR1 inhibits PfPP1 activity. Functional studies in Xenopus oocytes revealed that PfLRR1 interacted with endogenous PP1 and overcame the G2/M cell cycle checkpoint by promoting progression to germinal vesicle breakdown (GVBD). Confirmatory results showing the appearance of GVBD were observed when oocytes were treated with anti-PP1 antibodies or okadaic acid. Taken together, these observations suggest that PfLRR1 can regulate the cell cycle by binding to PP1 and regulating its activity.
名为“dis2突变体抑制因子（sds22+）”的蛋白质是裂殖酵母和芽殖酵母细胞分裂的重要调节因子，缺失该蛋白会导致有丝分裂停滞。在粟酒裂殖酵母中，其在细胞周期控制中的作用似乎是通过激活1型蛋白磷酸酶（PP1）来介导的。我们鉴定出了恶性疟原虫Sds22的直系同源物，因其属于富含亮氨酸重复序列蛋白家族，故将其命名为PfLRR1。我们通过谷胱甘肽-S-转移酶下拉实验表明，PfLRR1基因产物与PfPP1相互作用，PfLRR1-PfPP1复合物存在于寄生虫提取物中，且PfLRR1抑制PfPP1活性。非洲爪蟾卵母细胞的功能研究表明，PfLRR1与内源性PP1相互作用，并通过促进向生发泡破裂（GVBD）的进程来克服G2/M细胞周期检查点。当用抗PP1抗体或冈田酸处理卵母细胞时，观察到了显示GVBD出现的证实性结果。综上所述，这些观察结果表明，PfLRR1可通过与PP1结合并调节其活性来调控细胞周期。
