Functional and direct interaction between the RNA binding protein HuD and active Akt1.
Functional and direct interaction between the RNA binding protein HuD and active Akt1.
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DOI：
10.1093/nar/gkr979
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发表时间：
2012-03
影响因子：
14.9
通讯作者：
Sakamoto H
中科院分区：
文献类型：
--
作者：
Fujiwara T;Fukao A;Sasano Y;Matsuzaki H;Kikkawa U;Imataka H;Inoue K;Endo S;Sonenberg N;Thoma C;Sakamoto H
RNA结合蛋白HuD在神经元发育和可塑性中起着重要作用。我们之前已经证明，HUD刺激翻译。这种增强子功能的关键是HuD的接头区和poly（A）结合结构域，这对其在神经突生长中的功能也至关重要。在这里，我们进一步探索了潜在的分子相互作用，发现HuD而不是普遍表达的HuR直接与活性Akt 1相互作用。我们确定HuD的连接区是这种相互作用所必需的。我们还表明，通过使用嵌合突变体的HuD和HuR，其中包含RNA结合结构域2（RBD 2）和RBD 3之间的相互连接，分别，并通过过表达的显性负突变体的Akt 1的HuD-Akt 1的相互作用是功能上重要的，因为它是所需的诱导PC 12细胞中的神经突生长。这些结果表明，RNA结合的HuD作为一个适配器的功能，以招募Akt 1触发神经突生长的模型。这些数据也可能有助于解释HuD如何增强编码参与神经元发育的蛋白质的mRNA的翻译。
The RNA binding protein HuD plays essential roles in neuronal development and plasticity. We have previously shown that HuD stimulates translation. Key for this enhancer function is the linker region and the poly(A) binding domain of HuD that are also critical for its function in neurite outgrowth. Here, we further explored the underlying molecular interactions and found that HuD but not the ubiquitously expressed HuR interacts directly with active Akt1. We identify that the linker region of HuD is required for this interaction. We also show by using chimeric mutants of HuD and HuR, which contain the reciprocal linker between RNA-binding domain 2 (RBD2) and RBD3, respectively, and by overexpressing a dominant negative mutant of Akt1 that the HuD–Akt1 interaction is functionally important, as it is required for the induction of neurite outgrowth in PC12 cells. These results suggest the model whereby RNA-bound HuD functions as an adapter to recruit Akt1 to trigger neurite outgrowth. These data might also help to explain how HuD enhances translation of mRNAs that encode proteins involved in neuronal development.
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影响因子：
2.7
作者：
Matsuzaki, H;Ichino, A;Kikkawa, U
通讯作者：
Kikkawa, U
影响因子：
11.4
作者：
Raught, B;Peiretti, F;Hershey, JWB
通讯作者：
Hershey, JWB
DOI：
10.1016/j.bbrc.2004.06.140
发表时间：
2004-08-20
影响因子：
3.1
作者：
Saito, K;Fujiwara, T;Sakamoto, H
通讯作者：
Sakamoto, H
影响因子：
11.4
作者：
ALTMANN, M;MULLER, PP;TRACHSEL, H
通讯作者：
TRACHSEL, H
影响因子：
64.5
作者：
Sonenberg N;Hinnebusch AG
通讯作者：
Hinnebusch AG