Law Warren J, Cann Kendra L, Hicks Geoffrey G
Manitoba Institute of Cell Biology and the University of Manitoba, 675 McDermot Avenue, Winnipeg, MB, Canada.
Brief Funct Genomic Proteomic. 2006 Mar;5(1):8-14. doi: 10.1093/bfgp/ell015. Epub 2006 Feb 23.
Multifunctional proteins are demonstrating that gene expression is not a series of compartmentalized events beginning with transcription and culminating in delivery of mature mRNA into the cytoplasm, but an integrated pathway of transcription, splicing, RNA metabolism and subcellular targeting of translation. One such multifunctional family is made up of the RNA-binding proteins TLS, EWS and TAF15. These three proteins each contribute a potent transcriptional activation domain to oncogenic fusion proteins, and the formation of these fusion genes are thought to be the primary causes of their associated cancers. Wild-type TLS, EWS and TAF15 can function as classical transcription factors in addition to their better-known functions in splicing and mRNA transport. The interaction between TLS and the stress-response protein YB-1 is an example of how these proteins can induce a multi-faceted change in gene expression, as they can interact to induce changes in both transcription and splicing of target genes. Investigating the multiple functions of TLS, EWS and TAF15 will enhance our understanding of gene expression as a whole, and also allow us to better understand how these proteins may be contributing to the oncogenic pathways the associated fusion proteins initiate.
多功能蛋白表明基因表达并非是一系列从转录开始、以将成熟mRNA转运至细胞质为终点的分隔事件，而是转录、剪接、RNA代谢及翻译的亚细胞靶向的整合途径。其中一个这样的多功能家族由RNA结合蛋白TLS、EWS和TAF15组成。这三种蛋白各自为致癌融合蛋白贡献一个强效转录激活结构域，并且这些融合基因的形成被认为是其相关癌症的主要病因。野生型TLS、EWS和TAF15除了在剪接和mRNA转运中广为人知的功能外，还可作为经典转录因子发挥作用。TLS与应激反应蛋白YB-1之间的相互作用是这些蛋白如何能在基因表达中诱导多方面变化的一个例子，因为它们相互作用可诱导靶基因转录和剪接的变化。研究TLS、EWS和TAF15的多种功能将增进我们对整体基因表达的理解，也使我们能更好地理解这些蛋白如何可能促成相关融合蛋白所启动的致癌途径。
