mTORC2 can associate with ribosomes to promote cotranslational phosphorylation and stability of nascent Akt polypeptide
mTORC2 can associate with ribosomes to promote cotranslational phosphorylation and stability of nascent Akt polypeptide
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DOI：
10.1038/emboj.2010.271
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发表时间：
2010-12-01
期刊：
影响因子：
11.4
通讯作者：
Jacinto, Estela
中科院分区：
文献类型：
--
作者：
Oh, Won Jun;Wu, Chang-chih;Jacinto, Estela
在高等真核生物中，翻译和蛋白质加工的耦合机制尚不清楚。尽管哺乳动物雷帕霉素靶蛋白（mTOR）复合物1 （mTORC1）控制翻译起始，但mTORC2在蛋白质合成中的功能仍有待明确。在这项研究中，我们发现mTORC2可以与主动翻译的核糖体共定位，并可以稳定地与rpL23a相互作用，rpL23a是隧道出口存在的一个大的核糖体亚基蛋白。仅在Akt翻译过程中，mTORC2介导旋转基序（TM）位点Thr450的新生多肽磷酸化，以避免共翻译Akt泛素化。组成性TM磷酸化发生是因为TM位点是可接近的，而疏水基序列（Ser473）位点隐藏在核糖体隧道中。因此，mTORC2可以通过磷酸化新生链中的残基来发挥协同翻译的作用，这些残基对于获得正确的构象至关重要。我们的研究结果表明mTOR将蛋白质生产与质量控制联系起来。中国生物医学工程学报（2010）29,3939-3951。doi: 10.1038 / emboj.2010.271;2010年11月2日在线发布
The mechanisms that couple translation and protein processing are poorly understood in higher eukaryotes. Although mammalian target of rapamycin (mTOR) complex 1 (mTORC1) controls translation initiation, the function of mTORC2 in protein synthesis remains to be defined. In this study, we find that mTORC2 can colocalize with actively translating ribosomes and can stably interact with rpL23a, a large ribosomal subunit protein present at the tunnel exit. Exclusively during translation of Akt, mTORC2 mediates phosphorylation of the nascent polypeptide at the turn motif (TM) site, Thr450, to avoid cotranslational Akt ubiquitination. Constitutive TM phosphorylation occurs because the TM site is accessible, whereas the hydrophobic motif (Ser473) site is concealed in the ribosomal tunnel. Thus, mTORC2 can function cotranslationally by phosphorylating residues in nascent chains that are critical to attain proper conformation. Our findings reveal that mTOR links protein production with quality control. The EMBO Journal (2010) 29, 3939-3951. doi:10.1038/emboj.2010.271; Published online 2 November 2010