Liu Min and Chen Ruichuan's team published a paper in the journal "Nucleic Acids Research", revealing...

Recently, the team of Assistant Professor Liu Min and Professor Chen Ruichuan published a study titled "Disrupting the Cdk9/Cyclin T1 Heterodimer of 7SK snRNP for the Brd4 and AFF1/4 Guided Reconstitution of Active P-TEFb" in the journal "Nucleic Acids Research".
thesis
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This work reveals that during stress and cell cycle progression, the P-TEFb complex first dissociates completely into monomers, and then guides the process of re-formation and activation of the activated P-TEFb complex through the recruitment factors Brd4 and SEC, thereby regulating global genes.

Transcription elongation of eukaryotic genes is tightly and finely regulated, and its core regulatory element is the positive transcription elongation factor P-TEFb complex
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The core of the P-TEFb complex is a heterodimer formed by the kinase Cdk9 and the accessory protein CycT1; the core P-TEFb further forms a transcriptionally inactive 7SK snRNP complex in cells (i.

In this study, the team found for the first time that P-TEFb released upon dissociation of the transcriptionally inactive 7SK snRNP complex during stress and cell cycle progression did not exist as a complete heterodimer, but dissociated synchronously into T186 Dephosphorylated Cdk9 monomers and CycT1 monomers terminate the activity of transcriptional regulation in a completely "dead" (disintegrated) manner; the refinement of this process has benefited from improved nuclear extract fractionation techniques
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Since phosphorylation at the T186 site of the kinase Cdk9 determines the transcriptional regulatory activity of core P-TEFb, the "resurrection" of P-TEFb to form the activation complex must undergo reassembly of core P-TEFb and rephosphorylation at T186

The most surprising finding in this study is the complete disassembly of the core P-TEFb that has been dephosphorylated at T186 and has no transcriptional activity, which suggests that the activity regulation of the core transcriptional regulatory elements in cells is very fine and complex.
Tightly control the activity of gene transcription under physiological and stressful situations
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At the same time, the new concept that Cdk9 T186 must rely on the interaction with Brd4 and SEC for autophosphorylation interprets the mechanism of how Cdk9 kinase activity is activated, which has not been solved for more than ten years in the field of P-TEFb research

The co-first authors of the paper are Ph.
D.
students Kai Zhou, Songkuan Zhuang, and Futaki Liu, and Ph.
D.
student Yanheng Chen from the University of Illinois.
The corresponding authors are Assistant Professor Liu Min, Professor Chen Ruichuan, and Professor Chen Linfeng from the University of Illinois
.

The research work was supported by the National Natural Science Foundation of China, the NSFC-NIH Joint Funding Project, the Natural Science Foundation of Fujian Province, and the President's Fund of Xiamen University

Paper link: https://academic.

(Photo/Wen Chen Ruichuan's research group)