An evolutionarily conserved interaction of tumor suppressor protein Pdcd4 with the poly(A)-binding protein contributes to translation suppression by Pdcd4.
An evolutionarily conserved interaction of tumor suppressor protein Pdcd4 with the poly(A)-binding protein contributes to translation suppression by Pdcd4.
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DOI：
10.1093/nar/gku800
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发表时间：
2014
影响因子：
14.9
通讯作者：
Klempnauer KH
中科院分区：
文献类型：
--
作者：
Fehler O;Singh P;Haas A;Ulrich D;Müller JP;Ohnheiser J;Klempnauer KH
肿瘤抑制蛋白程序性细胞死亡4 （Pdcd4）与特定mrna的翻译调控有关，然而，天然Pdcd4靶mrna的身份以及Pdcd4影响其翻译的机制尚不清楚。Pdcd4结合真核生物翻译起始因子eIF4A并抑制其解旋酶活性，这表明Pdcd4抑制含有结构5 ' -非翻译区mrna的翻译起始。最近的研究揭示了第二种抑制机制，该机制不依赖于eif4a，涉及Pdcd4与靶mrna的直接rna结合。我们现在已经确定了聚(A)结合蛋白（PABP）作为Pdcd4的一种新的直接相互作用伙伴。与PABP相互作用的能力在人类和果蝇Pdcd4之间共享，表明它在进化过程中高度保守。失去与PABP相互作用能力的Pdcd4突变体在蔗糖密度梯度中不能稳定地与核糖体复合物结合并抑制翻译，例如c-myb mRNA。总的来说，我们的工作确定了PABP是一种新的功能相关的Pdcd4相互作用伙伴，有助于调节Pdcd4的翻译。
The tumor suppressor protein programmed cell death 4 (Pdcd4) has been implicated in the translational regulation of specific mRNAs, however, the identities of the natural Pdcd4 target mRNAs and the mechanisms by which Pdcd4 affects their translation are not well understood. Pdcd4 binds to the eukaryotic translation initiation factor eIF4A and inhibits its helicase activity, which has suggested that Pdcd4 suppresses translation initiation of mRNAs containing structured 5′-untranslated regions. Recent work has revealed a second inhibitory mechanism, which is eIF4A-independent and involves direct RNA-binding of Pdcd4 to the target mRNAs. We have now identified the poly(A)-binding protein (PABP) as a novel direct interaction partner of Pdcd4. The ability to interact with PABP is shared between human and Drosophila Pdcd4, indicating that it has been highly conserved during evolution. Mutants of Pdcd4 that have lost the ability to interact with PABP fail to stably associate with ribosomal complexes in sucrose density gradients and to suppress translation, as exemplified by c-myb mRNA. Overall, our work identifies PABP as a novel functionally relevant Pdcd4 interaction partner that contributes to the regulation of translation by Pdcd4.
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作者：
Mangus, David A;Evans, Matthew C;Jacobson, Allan
通讯作者：
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