Oncogenic partnerships: EWS-FLI1 protein interactions initiate key pathways of Ewing's sarcoma.
Oncogenic partnerships: EWS-FLI1 protein interactions initiate key pathways of Ewing's sarcoma.
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DOI：
10.1158/1078-0432.ccr-09-2261
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发表时间：
2010-08-15
期刊：
影响因子：
--
通讯作者：
Toretsky JA
中科院分区：
文献类型：
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作者：
Erkizan HV;Uversky VN;Toretsky JA
癌症的靶向治疗是治疗的黄金标准，它专门针对癌症，没有任何控制肿瘤以外的潜在影响。尤文氏肉瘤含有潜在的目标EWS-FLI 1，作为一种特异性染色体易位的结果。EWS-FLI 1融合蛋白包括EWS结构域，一种有效的转录激活因子，以及高度保守的FLI 1 ets DNA结合结构域。由于这些结构域的组合，EWS-FLI 1融合蛋白充当异常转录因子，其表达导致细胞转化。EWS-FLI 1通过在转录和剪接中与正常细胞蛋白质伴侣结合来发挥作用，类似于病毒如何破坏正常细胞机制以产生病毒体。因此，了解EWS-FLI 1的蛋白质-蛋白质相互作用以及由这些伙伴关系调节的途径将为肿瘤发生和治疗提供信息。本文综述了EWS-FLI 1已知的蛋白质伴侣和转录靶点，同时提出了利用这些伙伴关系进行靶向治疗的策略。
Targeted therapy for cancer, which is specifically directed toward the cancer without any potential for effects outside of controlling the tumor, is a gold standard for treatment. Ewing’s sarcoma contains the potential target EWS-FLI1, as a result of a pathognomonic chromosomal translocation. The EWS-FLI1 fusion protein includes the EWS domain, a potent transcriptional activator alongside the highly conserved FLI1 ets DNA-binding domain. Because of the combination of these domains, the EWS-FLI1 fusion protein acts as an aberrant transcription factor whose expression results in cellular transformation. EWS-FLI1 functions by binding to normal cellular protein partners in transcription and splicing, similar to how a virus would corrupt normal cellular machinery for virion production. Therefore, understanding the protein-protein interactions of EWS-FLI1 and the pathways that are regulated by these partnerships will inform both oncogenesis and therapeutics. This review describes the known protein partners and transcriptional targets of EWS-FLI1, while proposing strategies for exploiting these partnerships with targeted therapy.