Ribosomal protein uL3 targets E2F1 and Cyclin D1 in cancer cell response to nucleolar stress
Ribosomal protein uL3 targets E2F1 and Cyclin D1 in cancer cell response to nucleolar stress
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DOI：
10.1038/s41598-019-51723-7
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发表时间：
2019-10-28
影响因子：
4.6
通讯作者：
Russo, Annapina
中科院分区：
文献类型：
--
作者：
Pecoraro, Annalisa;Carotenuto, Pietro;Russo, Annapina
癌症治疗中的几种实验策略包括细胞周期调节途径的药物改变作为有用的策略。人核糖体蛋白L3（uL 3）的核糖体外功能可能影响DNA修复、细胞周期阻滞和凋亡。在本研究中，我们证明了uL 3是激活G1/S转换基因所必需的。荧光素酶分析证实uL 3负调控E2 F1启动子的活性。诱导的无核糖体uL 3降低细胞周期蛋白D1 mRNA和蛋白水平。使用蛋白质/蛋白质免疫沉淀方法，我们证明了uL 3与PARP-1的物理相互作用影响E2 F1的转录活性。我们的研究结果导致了一个新的途径的鉴定uL 3介导的E2 F1和细胞周期蛋白D1在调节细胞周期进程。
Several experimental strategies in the treatment of cancer include drug alteration of cell cycle regulatory pathways as a useful strategy. Extra-ribosomal functions of human ribosomal protein L3 (uL3) may affect DNA repair, cell cycle arrest and apoptosis. In the present study, we demonstrated that uL3 is required for the activation of G1/S transition genes. Luciferase assays established that uL3 negatively regulates the activity of E2F1 promoter. Induced ribosome-free uL3 reduces Cyclin D1 mRNA and protein levels. Using protein/protein immunoprecipitation methods, we demonstrated that uL3 physically interacts with PARP-1 affecting E2F1 transcriptional activity. Our findings led to the identification of a new pathway mediated by uL3 involving E2F1 and Cyclin D1 in the regulation of cell cycle progression.