AMPK represses TOP mRNA translation but not global protein synthesis in liver.
AMPK represses TOP mRNA translation but not global protein synthesis in liver.
复制标题
AMPK 抑制 TOP mRNA 翻译，但不抑制肝脏中整体蛋白质合成。
DOI：
10.1016/j.bbrc.2008.07.025
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发表时间：
2008
影响因子：
3.1
通讯作者：
Jefferson,LeonardS
中科院分区：
文献类型：
--
作者：
Reiter,AliK;Bolster,DouglasR;Crozier,StephenJ;Kimball,ScotR;Jefferson,LeonardS
AMP 激活蛋白激酶 (AMPK) 通过哺乳动物雷帕霉素复合物靶标 1 (mTORC1) 抑制信号传导。在肌肉中，mTORC1 的抑制会导致整体蛋白质合成减少。相比之下，肝脏中 mTORC1 的抑制对整体蛋白质合成没有立即影响。在本研究中，通过 mTORC1 的信号传导和特定 mRNA 的翻译，例如带有 5' 末端寡嘧啶 (TOP) 束的 mRNA 的翻译，并在跑步机跑步后 AMPK 激活后在大鼠肝脏中进行了检查。 AMPK 的激活抑制了编码 rpS6、rpS8 和 eEF1α 的 TOP mRNA 的翻译。相比之下，编码 GAPDH 或 β-肌动蛋白的 mRNA 的整体蛋白质合成和翻译都没有改变。 AMPK 激活后，mTORC1 靶标 4E-BP1（而非 S6K1 或 rpS6）的基础磷酸化降低。因此，在肝脏中，AMPK 激活通过与 S6K1 或 rpS6 磷酸化下调不同的机制抑制 TOP mRNA 的翻译。
The AMP-activated protein kinase (AMPK) represses signaling through the mammalian target of rapamycin complex 1 (mTORC1). In muscle, repression of mTORC1 leads to a reduction in global protein synthesis. In contrast, repression of mTORC1 in the liver has no immediate effect on global protein synthesis. In the present study, signaling through mTORC1 and translation of specific mRNAs such as those bearing a 5′-terminal oligopyrimidine (TOP) tract and were examined in rat liver following activation of AMPK after treadmill running. Activation of AMPK repressed translation of the TOP mRNAs encoding rpS6, rpS8, and eEF1α. In contrast, neither global protein synthesis nor translation of mRNAs encoding GAPDH or β-actin was changed. Basal phosphorylation of the mTORC1 target 4E-BP1, but not S6K1 or rpS6, was reduced following activation of AMPK. Thus, in liver, AMPK activation repressed translation of TOP mRNAs through a mechanism distinct from downregulated phosphorylation of S6K1 or rpS6.