Detailseite
Projekt Druckansicht

Struktur- und Funktionsanalyse der Transkriptions-regulierenden Kinasen Cdk10 und Cdk11

Fachliche Zuordnung Biochemie
Förderung Förderung von 2012 bis 2021
Projektkennung Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 226824387
 
Erstellungsjahr 2022

Zusammenfassung der Projektergebnisse

For the first topic of our research grant, we were able to provide a detailed analysis of Cdk10 substrate specificity and function. Using recombinant, full length Cdk10/CycQ protein complexes including T-loop mutants we show that Cdk10 phosphorylation at Thr196 is dispensable for complex formation with CycQ but critical for kinase activity. We identify RNA pol II CTD, c-MYC and Rb1 as in vitro substrates of Cdk10/CycQ and show that Cdk10 exhibits a strong site-specific activity for Ser2 within the CTD repeats. Based on our data and previous studies we speculate that Cdk10 obtains a hybrid position between cell cycle and transcriptional CDKs and acts as an integrator of external and internal stimuli such as cell stress, growth factors or DNA damage. We still follow up crystallization trials of Cdk10/CycQ, including a specific nanobody and inhibiting small molecular compounds. The work on the Cdk11 kinases with their cyclin partners L1 and L2 is still ongoing. We are currently following several paths to gain a stable Cdk11/CycL complex, characterize the ability for LLPS formation and generate nanobodies to stabilize the kinase for crystallization trials. A couple of contributions that remained from the first funding period or demanded our expertise in recombinant protein purification turned out to be scientifically very fruitful. This included the production of bacterial polymerases and a reverse transcriptase as well as kinase dose response measurements.

Projektbezogene Publikationen (Auswahl)

 
 

Zusatzinformationen

Textvergrößerung und Kontrastanpassung