Therapeutic interventions to disrupt the protein synthetic machinery in melanoma.
Therapeutic interventions to disrupt the protein synthetic machinery in melanoma.
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DOI：
10.1111/pcmr.12391
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发表时间：
2015-09
影响因子：
4.3
通讯作者：
Robertson GP
中科院分区：
文献类型：
--
作者：
Kardos GR;Robertson GP
在包括黑色素瘤在内的许多癌症中，蛋白质合成机制的控制被放松，以增加蛋白质的产生。肿瘤抑制基因和癌基因在蛋白质合成中起着关键作用，从rRNA和核糖体的生物合成到mRNA的翻译起始和蛋白质合成。黑色素瘤中的主要信号通路被改变，以调节蛋白质合成机制，从而促进肿瘤的发展。然而，尽管这一过程在黑色素瘤的发展中很重要，但蛋白质合成机制在这种癌症类型中的参与是一个不发达的研究领域。在这里，我们回顾了黑色素瘤的发展与蛋白质合成机制的放松之间的耦合。我们考察了关于RNA聚合酶I抑制和mRNA翻译的现有知识，重点是它们对黑色素瘤治疗应用的抑制。此外，氨基酸生物合成的贡献和核糖体蛋白的参与也被认为是针对黑色素瘤非调控蛋白生产的未来治疗策略。
Control of the protein synthetic machinery is deregulated in many cancers, including melanoma, in order to increase protein production. Tumor suppressors and oncogenes play key roles in protein synthesis from the transcription of rRNA and ribosome biogenesis to mRNA translation initiation and protein synthesis. Major signaling pathways are altered in melanoma to modulate the protein synthetic machinery thereby promoting tumor development. However, despite the importance of this process in melanoma development, involvement of the protein synthetic machinery in this cancer type is an underdeveloped area of study. Here, we review the coupling of melanoma development to deregulation of the protein synthetic machinery. We examine existing knowledge regarding RNA Polymerase I inhibition and mRNA translation focusing on their inhibition for therapeutic applications in melanoma. Furthermore, the contribution of amino acid biosynthesis and involvement of ribosomal proteins are also reviewed as future therapeutic strategies to target deregulated protein production in melanoma.