eIF3a regulation of mTOR signaling and translational control via HuR in cellular response to DNA damage.
eIF3a regulation of mTOR signaling and translational control via HuR in cellular response to DNA damage.
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eIF3a通过HuR调控mTOR信号和翻译调控细胞对DNA损伤的反应。
DOI：
10.1038/s41388-022-02262-5
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发表时间：
2022-04
期刊：
影响因子：
8
通讯作者：
Zhang, Jian-Ting
中科院分区：
文献类型：
--
作者：
Ma, Shijie;Dong, Zizheng;Huang, Yanfei;Liu, Jing-Yuan;Zhang, Jian-Ting
eIF 3a（真核生物翻译起始因子3a）是eIF 3复合物的一个亚基，已被认为在蛋白质合成和细胞对DNA损伤处理的反应中起调节作用。S6 K1是mTOR复合物1（mTORC 1）的效应子和介导子，在调节蛋白质合成和整合多种信号以控制细胞生长和应激反应中起作用。在这里，我们表明eIF 3a通过调节Raptor合成抑制mTORC 1激酶来调节S6 K1活性。Raptor合成的调节是通过eIF 3a与HuR（人抗原R）的相互作用以及eIF 3a-HuR复合物与Raptor mRNA的5 '-UTR的结合。此外，mTORC 1可能通过调节NER蛋白的合成和NER活性来介导eIF 3a对顺铂的细胞应答功能。综上所述，我们得出结论，mTOR信号通路也可能受到翻译控制的调节，并通过调节NER蛋白合成介导eIF 3a调节癌细胞对顺铂的反应。
eIF3a (eukaryotic translation initiation factor 3a), a subunit of the eIF3 complex, has been suggested to play a regulatory role in protein synthesis and in cellular response to DNA-damaging treatments. S6K1 is an effector and a mediator of mTOR complex1 (mTORC1) in regulating protein synthesis and integrating diverse signals into control of cell growth and response to stress. Here, we show that eIF3a regulates S6K1 activity by inhibiting mTORC1 kinase via regulating Raptor synthesis. The regulation of Raptor synthesis is via eIF3a interaction with HuR (human antigen R) and binding of the eIF3a-HuR complex to the 5’-UTR of Raptor mRNA. Furthermore, mTORC1 may mediate eIF3a function in cellular response to cisplatin by regulating synthesis of NER proteins and NER activity. Taken together, we conclude that the mTOR signaling pathway may also be regulated by translational control and mediate eIF3a regulation of cancer cell response to cisplatin by regulating NER protein synthesis.
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影响因子：
8.1
作者：
Kocalis HE;Hagan SL;George L;Turney MK;Siuta MA;Laryea GN;Morris LC;Muglia LJ;Printz RL;Stanwood GD;Niswender KD
通讯作者：
Niswender KD
影响因子：
16
作者：
Kim, DH;Sarbassov, DD;Sabatini, DM
通讯作者：
Sabatini, DM
eIF3a通过调节DSB DNA修复对蒽环类化疗耐药的影响
影响因子：
5.8
作者：
Chen, Juan;Liu, Jun-Yan;Yin, Ji-Ye
通讯作者：
Yin, Ji-Ye
影响因子：
7.4
作者：
Babichev Y;Kabaroff L;Datti A;Uehling D;Isaac M;Al-Awar R;Prakesch M;Sun RX;Boutros PC;Venier R;Dickson BC;Gladdy RA
通讯作者：
Gladdy RA
影响因子：
4.8
作者：
Carriere, Audrey;Romeo, Yves;Roux, Philippe P.
通讯作者：
Roux, Philippe P.