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biomill8358

无虫 (小有名气)

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注册: 2009-01-08

[交流] 【分享】RNA 结合蛋白HuR通过刺激XIAP的翻译而介导的细胞保护已有1人参与

RNA-binding protein HuRmediates cytoprotectionthrough stimulation of XIAP translation
RNA 结合蛋白HuR通过刺激XIAP的翻译而介导的细胞保护
DDurie1,2, S MLewis1,5, ULiwak1,2, MKisilewicz1,2, MGorospe4 and MHolcik
Oncogene(2011) 30, 1460–1469; doi:10.1038/onc.2010.527; published online 22 November 2010
摘要：Expression of the intrinsic cellular caspaseinhibitor XIAP is regulated primarily at the level of protein synthesis. The 5′untranslatedregion harboursan Internal Ribosome Entry Site (IRES) motif that supports cap-independent translation of XIAP mRNA during conditions of cellular stress. In this study, we show that the RNA-binding protein HuR, which is known to orchestrate an antiapoptoticcellular program, stimulates translation of XIAP mRNA through XIAP IRES. We further show that HuRbinds to XIAP IRES in vitroand in vivo, and stimulates recruitment of the XIAP mRNA into polysomes. Importantly, protection from the apoptosis-inducing agent etoposideby overexpressionof HuRrequires the presence of XIAP, suggesting that HuR-mediated cytoprotectionis partially executed through enhanced XIAP translation. Our data suggest that XIAP belongs to the HuR-regulated RNA operonof antiapoptoticgenes, which, along with Bcl-2, Mcl-1 and ProTα, contributes to the regulation of cell survival.
1.细胞固有的caspase抑制物XIAP的表达主要在蛋白合成的水平上受到调控。5′UTR区有一个内部核糖体进入位点（IRES）结构域，它为在细胞压力条件下，XIAP mRNA帽子依赖的翻译提供了支持。
2.本研究中，我们展示了RNA结合蛋白HuR，一种协调细胞抗凋亡程序的蛋白，通过XIAP的IRES刺激XIAP mRNA的翻译。进一步展示了HuR在体内外与XIAP IRES的结合并刺激招募XIAP mRNA形成多聚体。
3.重要的是，过表达HuR抵抗引发凋亡的试剂依托泊甙需要XIAP的存在，暗示HuR介导的细胞保护作用部分的通过加强XIAP的翻译来执行。
4.我们的数据暗示XIAP属于HuR调节的抗凋亡基因的RNA操纵子，它与Bcl-2, Mcl-1 和ProTα一起有助于细胞生存的调控。
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