Degradation of Newly Synthesized Polypeptides by Ribosome-Associated RACK1/c-Jun N-Terminal Kinase/Eukaryotic Elongation Factor 1A2 Complex
Degradation of Newly Synthesized Polypeptides by Ribosome-Associated RACK1/c-Jun N-Terminal Kinase/Eukaryotic Elongation Factor 1A2 Complex
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DOI：
10.1128/mcb.01362-12
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发表时间：
2013-07-01
影响因子：
5.3
通讯作者：
Ronaic, Ze'ev A.
中科院分区：
文献类型：
--
作者：
Gandin, Valentina;Gutierrez, Gustavo J.;Ronaic, Ze'ev A.
新合成的多肽（NSP）折叠成功能蛋白是一个高度调控的过程。严格的质量控制确保NSP在翻译过程中或完成后不久获得其天然折叠。尽管如此，控制哺乳动物中NSP降解的信号通路仍然难以捉摸。我们证明，应激诱导的c-Jun N-末端激酶（JNK）被激活的蛋白C激酶1（RACK 1）受体募集到核糖体。RACK 1是40 S核糖体的组成部分，也是蛋白激酶的接头。核糖体相关JNK磷酸化丝氨酸205和358上的真核翻译延伸因子1A同种型2（eEF 1A 2）以促进蛋白酶体降解NSP。这些发现确立了RACK 1/JNK/eEF 1A 2复合物在响应压力的NSP的质量控制中的作用。
Folding of newly synthesized polypeptides (NSPs) into functional proteins is a highly regulated process. Rigorous quality control ensures that NSPs attain their native fold during or shortly after completion of translation. Nonetheless, signaling pathways that govern the degradation of NSPs in mammals remain elusive. We demonstrate that the stress-induced c-Jun N-terminal kinase (JNK) is recruited to ribosomes by the receptor for activated protein C kinase 1 (RACK1). RACK1 is an integral component of the 40S ribosome and an adaptor for protein kinases. Ribosome-associated JNK phosphorylates the eukaryotic translation elongation factor 1A isoform 2 (eEF1A2) on serines 205 and 358 to promote degradation of NSPs by the proteasome. These findings establish a role for a RACK1/JNK/eEF1A2 complex in the quality control of NSPs in response to stress.