Novel role of CAP1 in regulation RNA polymerase II-mediated transcription elongation depends on its actin-depolymerization activity in nucleoplasm
Novel role of CAP1 in regulation RNA polymerase II-mediated transcription elongation depends on its actin-depolymerization activity in nucleoplasm
复制标题
CAP1 在调节 RNA 聚合酶 II 介导的转录延伸中的新作用取决于其核质中的肌动蛋白解聚活性
DOI：
10.1038/s41388-021-01789-3
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发表时间：
2021-04-28
期刊：
影响因子：
8
通讯作者：
Li，Guobing
中科院分区：
文献类型：
--
作者：
Zhang，Qian;Tang，Qin;Li，Guobing
肺癌是世界范围内发病率和死亡率都很高的疑难杂症之一。腺苷酸环化酶相关蛋白1（CAP 1）是一种著名的肌动蛋白解聚因子，最近被报道是一种促进癌细胞增殖的癌基因。然而，CAP 1在肺癌中的生理意义还不完全清楚，并且CAP 1在转录调控中的新功能仍然未知。我们发现CAP 1在肺癌组织和细胞中高表达，并且与肺癌患者的预后呈负相关。此外，CAP 1通过促进蛋白质合成加速细胞周期进程而促进A549细胞增殖。从机制上讲，我们发现，CAP 1促进细胞周期蛋白依赖性激酶9（CDK 9）介导的RNA聚合酶（Pol）II-Ser 2磷酸化和随后的转录延伸，和CAP 1执行其功能，在这一进程取决于其肌动蛋白解聚活性在核质。此外，我们的体内研究结果证实，CAP 1促进的A549异种移植肿瘤生长与CDK 9介导的Pol II-Ser 2磷酸化相关。我们的研究阐明了CAP 1通过促进聚合酶II磷酸化来调节转录的新作用，并表明CAP 1是一种新发现的肺癌治疗和预后预测的生物标志物。
Lung cancer is one of the most intractable diseases with high incidence and mortality worldwide. Adenylate cyclase-associated protein 1 (CAP1), a well-known actin depolymerization factor, is recently reported to be an oncogene accelerating cancer cell proliferation. However, the physiological significance of CAP1 in lung cancer is incompletely understood and the novel functions of CAP1 in transcriptional regulation remain unknown. Here we found that CAP1 was highly expressed in lung cancer tissues and cells, which was also negatively associated with prognosis in lung cancer patients. Moreover, CAP1 promoted A549 cells proliferation by promoting protein synthesis to accelerate cell cycle progression. Mechanistically, we revealed that CAP1 facilitated cyclin-dependent kinase 9 (CDK9)-mediated RNA polymerases (Pol) II-Ser2 phosphorylation and subsequent transcription elongation, and CAP1 performed its function in this progress depending on its actin-depolymerization activity in nucleoplasm. Furthermore, our in vivo findings confirmed that CAP1-promoted A549 xenograft tumor growth was associated with CDK9-mediated Pol II-Ser2 phosphorylation. Our study elucidates a novel role of CAP1 in modulating transcription by promoting polymerase II phosphorylation and suggests that CAP1 is a newly identified biomarker for lung cancer treatment and prognosis prediction.