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CDK12 and Integrator-PP2A complex modulates LEO1 phosphorylation for processive transcription elongation

Sci Adv. 2023-05; 
Min Qiu, Zhinang Yin, Honghong Wang, Lingyu Lei, Conghui Li, Yali Cui, Rong Dai, Peiyuan Yang, Ying Xiang, Qiuzi Li, Junhui Lv, Zhuang Hu, Min Chen, Hai-Bing Zhou, Pingping Fang, Ruijing Xiao, Kaiwei Liang
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Molecular Biology Reagents … The digested peptides were incubated with high-affinity iodoacetyl resin (GenScript, catalog no. L00403) on a shaker at room temperature for 5 hours. The resin was then washed once … Get A Quote

摘要

Cyclin-dependent kinase 12 (CDK12) interacts with cyclin K to form a functional nuclear kinase that promotes processive transcription elongation through phosphorylation of the C-terminal domain of RNA polymerase II (Pol II). To gain a comprehensive understanding of CDK12's cellular function, we used chemical genetic and phosphoproteomic screening to identify a landscape of nuclear human CDK12 substrates, including regulators of transcription, chromatin organization, and RNA splicing. We further validated LEO1, a subunit of the polymerase-associated factor 1 complex (PAF1C), as a bona fide cellular substrate of CDK12. Acute depletion of LEO1, or substituting LEO1 phosphorylation sites with alanine, attenuated PA... More

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