Adenovirus E4orf6 targets pp32/LANP to control the fate of ARE-containing mRNAs by perturbing the CRM1-dependent mechanism.
Adenovirus E4orf6 targets pp32/LANP to control the fate of ARE-containing mRNAs by perturbing the CRM1-dependent mechanism.
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DOI：
10.1083/jcb.200405112
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发表时间：
2005-07-04
期刊：
影响因子：
--
通讯作者：
Shindoh M
中科院分区：
文献类型：
--
作者：
Higashino F;Aoyagi M;Takahashi A;Ishino M;Taoka M;Isobe T;Kobayashi M;Totsuka Y;Kohgo T;Shindoh M
E4 orf 6在细胞和病毒mRNA的转运中起重要作用，并且被认为是腺病毒的癌基因产物。在这里，我们表明，E4 orf 6与pp 32/富含亮氨酸的酸性核蛋白（LANP）相互作用。E4 orf 6将pp 32/LANP与其结合伴侣HuR一起从细胞核输出到细胞质，HuR与许多原癌基因和细胞因子mRNA中存在的富含AU的元件（ARE）结合。我们发现，ARE-mRNA，如c-fos，c-myc，和环氧合酶-2，也出口到并稳定在E4 orf 6表达细胞的细胞质中。E4 orf 6的原癌域是与pp 32/LANP结合和影响ARE-mRNA所必需的。C-fos mRNA与E4 orf 6、E1 B-55 kD、pp 32/LANP和HuR蛋白一起输出。此外，CRM 1依赖性输出途径的抑制未能阻断E4 orf 6介导的ARE-mRNA的输出。因此，E4 orf 6与pp 32/LANP相互作用，通过改变CRM 1依赖性输出途径来调节ARE-mRNA的命运。
E4orf6 plays an important role in the transportation of cellular and viral mRNAs and is known as an oncogene product of adenovirus. Here, we show that E4orf6 interacts with pp32/leucine-rich acidic nuclear protein (LANP). E4orf6 exports pp32/LANP from the nucleus to the cytoplasm with its binding partner, HuR, which binds to an AU-rich element (ARE) present within many protooncogene and cytokine mRNAs. We found that ARE-mRNAs, such as c-fos, c-myc, and cyclooxygenase-2, were also exported to and stabilized in the cytoplasm of E4orf6-expressing cells. The oncodomain of E4orf6 was necessary for both binding to pp32/LANP and effect for ARE-mRNA. C-fos mRNA was exported together with E4orf6, E1B-55kD, pp32/LANP, and HuR proteins. Moreover, inhibition of the CRM1-dependent export pathway failed to block the export of ARE-mRNAs mediated by E4orf6. Thus, E4orf6 interacts with pp32/LANP to modulate the fate of ARE-mRNAs by altering the CRM1-dependent export pathway.
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