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RACK1通过MCM7/RACK1/Akt信号复合物促进肺癌细胞生长。

RACK1 promotes lung cancer cell growth via an MCM7/RACK1/ Akt signaling complex.

作者信息

Fei Liangru, Ma Yinan, Zhang Meiyu, Liu Xiaofang, Luo Yuan, Wang Congcong, Zhang Haiyan, Zhang Wenzhu, Han Yuchen

机构信息

Department of Pathology, School of Basic Medical Sciences, China Medical University, Shenyang 110000, China.

Department of Pathology, The First Affiliated Hospital of China Medical University, Shenyang 110000, China.

出版信息

Oncotarget. 2017 Jun 20;8(25):40501-40513. doi: 10.18632/oncotarget.17120.

Abstract

MCM7, a member of the miniature chromosome maintenance (MCM) protein family, is crucial for the initiation of DNA replication and proliferation in eukaryotic cells. In this report, we demonstrate that RACK1 regulates cell growth and cell cycle progression in human non-small-cell lung cancer by mediating MCM7 phosphorylation through an MCM7/RACK1/Akt signaling complex. RACK1 functions as a central scaffold that brings Akt into physical proximity with MCM7. Overexpression of RACK1 increases interactions between Akt and MCM7 and promotes Akt-dependent MCM7 phosphorylation, which in turn increases MCM7 binding to chromatin and MCM complex formation. Together, these changes promote DNA replication and cell proliferation. Our findings reveal a novel signaling pathway that regulates growth in non-small cell lung cancer.

摘要

MCM7是微小染色体维持(MCM)蛋白家族的成员之一,对真核细胞中DNA复制的起始和增殖至关重要。在本报告中,我们证明RACK1通过MCM7/RACK1/Akt信号复合物介导MCM7磷酸化,从而调节人非小细胞肺癌中的细胞生长和细胞周期进程。RACK1作为一个核心支架,使Akt与MCM7在物理上接近。RACK1的过表达增加了Akt与MCM7之间的相互作用,并促进了Akt依赖性的MCM7磷酸化,这反过来又增加了MCM7与染色质的结合以及MCM复合物的形成。这些变化共同促进了DNA复制和细胞增殖。我们的研究结果揭示了一种调节非小细胞肺癌生长的新信号通路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d836/5522230/992265a76077/oncotarget-08-40501-g001.jpg

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