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  Functional characterization of the human Cdk10/Cyclin Q complex

Düster, R., Ji, Y., Pan, K.-T., Urlaub, H., & Geyer, M. (2022). Functional characterization of the human Cdk10/Cyclin Q complex. Open Biology, 12(3): 210381. doi:10.1098/rsob.210381.

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Düster, R., Author
Ji, Y.1, Author              
Pan, K.-T., Author
Urlaub, H.1, Author              
Geyer, M., Author
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1Research Group of Bioanalytical Mass Spectrometry, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society, ou_3350290              

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Free keywords: transcription, cell cycle, CDK10, Cyclin Q, Cyclin M, RNA polymerase II
 Abstract: Cyclin-dependent kinases (CDKs) are key players in cell cycle regulation and transcription. The CDK-family member Cdk10 is important for neural development and can act as a tumour suppressor, but the underlying molecular mechanisms are largely unknown. Here, we provide an in-depth analysis of Cdk10 substrate specificity and function. Using recombinant Cdk10/CycQ protein complexes, we characterize RNA pol II CTD, c-MYC and RB1 as in vitro protein substrates. Using an analogue-sensitive mutant kinase, we identify 89 different Cdk10 phosphosites in HEK cells originating from 66 different proteins. Among these, proteins involved in cell cycle, translation, stress response, growth signalling, as well as rRNA, and mRNA transcriptional regulation, are found. Of a set of pan-selective CDK- and Cdk9-specific inhibitors tested, all inhibited Cdk10/CycQ at least five times weaker than their proposed target kinases. We also identify Cdk10 as an in vitro substrate of Cdk1 and Cdk5 at multiple sites, allowing for a potential cross-talk between these CDKs. With this functional characterization, Cdk10 adopts a hybrid position in both cell cycle and transcriptional regulation.

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Language(s): eng - English
 Dates: 2022-03-16
 Publication Status: Published online
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1098/rsob.210381
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Title: Open Biology
Source Genre: Journal
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Pages: 17 Volume / Issue: 12 (3) Sequence Number: 210381 Start / End Page: - Identifier: ISSN: 2046-2441