Translation of TRAF1 is regulated by IRES-dependent mechanism and stimulated by vincristine.

Translation of TRAF1 is regulated by IRES-dependent mechanism and stimulated by vincristine.
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DOI:
10.1093/nar/gkq183
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发表时间:
2010-07
影响因子:
14.9
通讯作者:
Zhou M
Zhou M
中科院分区:
生物学2区
文献类型:
--
作者:
Yang L;Gu L;Li Z;Zhou M

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TRAF1是TRAF家族的成员,在免疫反应、炎症和恶性疾病中介导细胞生死的信号转导中发挥重要作用。众所周知,TRAF1 转录可由多种细胞因子诱导,但对其 mRNA 翻译的调控知之甚少。在本研究中,我们证明人类 TRAF1 mRNA 具有异常长的 5'-UTR,其中包含调节其翻译的内部核糖体进入片段 (IRES)。通过进行基因转染和报告基因检测,我们发现该 IRES 序列位于 AUG 起始密码子上游 572 nt 处。 nt -392 和 -322 之间的元素对于 IRES 活性至关重要。有趣的是,我们发现化疗药物长春新碱在癌细胞中诱导TRAF1表达,调节多嘧啶束结合蛋白的细胞质定位,这可能有助于长春新碱治疗期间TRAF1的IRES依赖性翻译。这些结果表明TRAF1翻译是通过IRES启动并受长春新碱调节的,并且表明TRAF1的IRES依赖性翻译的调节可能参与影响癌细胞对长春新碱治疗的反应。
TRAF1 is a member of the TRAF family, which plays important roles in signal transduction that mediate cell life and death in the immune response, inflammatory and malignant diseases. It is known that TRAF1 transcription is inducible by various cytokines, but little is known about the regulation of its mRNA translation. In the present study, we demonstrated that the human TRAF1 mRNA has an unusually long 5′-UTR that contains internal ribosome entry segment (IRES) regulating its translation. By performing gene transfection and reporter assays, we revealed that this IRES sequence is located within the 572 nt upstream from the AUG start codon. An element between nt −392 and −322 was essential for the IRES activity. Interestingly, we found that the TRAF1 expression is induced in cancer cells by chemotherapeutic drug vincristine that regulates cytoplasmic localization of polypyrimidine tract binding protein, which may contribute to the IRES-dependent translation of TRAF1 during vincristine treatment. These results indicate that TRAF1 translation is initiated via the IRES and regulated by vincristine, and suggest that regulation of the IRES-dependent translation of TRAF1 may be involved in effecting the cancer cell response to vincristine treatment.
在趋化应激后,BAG-1 IRES介导的翻译调节。
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