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全激酶组CRISPR-Cas9筛选揭示了其作为TGF-β信号传导的正向调节因子。

Kinome-wide CRISPR-Cas9 screens revealed as a positive regulator of TGF-β signaling.

作者信息

Wang Dingding, Zhang Xinhao, Guo Jianxun, Liu Weijia, Zhou Yanchi, Wang Renxian

机构信息

JST Sarcopenia Research Centre, National Center for Orthopaedics, Beijing Research Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, Capital Medical University, Beijing, 100035, China.

Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China.

出版信息

Biochem Biophys Rep. 2024 Nov 12;40:101864. doi: 10.1016/j.bbrep.2024.101864. eCollection 2024 Dec.

Abstract

The TGF-β signaling pathway is closely associated with human health and disease, and the systematic identification of factors involved in the TGF-β signaling pathway significantly contributes to the understanding and treatment of various diseases. Through kinome-wide CRISPR screen, we identified 13 candidate regulatory targets. Notably, the well-known hallmark genes and emerged as the top two candidate targets. and were ranked third and fourth as positive candidate targets, respectively, with being a novel discovery. Importantly, our findings revealed the down-regulation of and using CRISPR knockout and RNAi technology effectively suppressed the TGF-β signaling pathway in HeLa and HaCaT cells, providing new insights of TGF-β signaling.

摘要

转化生长因子-β(TGF-β)信号通路与人类健康和疾病密切相关,系统鉴定参与TGF-β信号通路的因子对理解和治疗各种疾病有显著贡献。通过全激酶组CRISPR筛选,我们鉴定出13个候选调控靶点。值得注意的是,著名的标志性基因和成为前两个候选靶点。和分别作为阳性候选靶点排名第三和第四,是一个新发现。重要的是,我们的研究结果表明,使用CRISPR敲除和RNAi技术下调和可有效抑制HeLa和HaCaT细胞中的TGF-β信号通路,为TGF-β信号通路提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4ba/11605321/2be4f9c15d46/gr1.jpg

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