Deep label free phosphoproteomics identifies novel mechanisms of kinase function.
Updated: Aug 14, 2020
RNA Polymerase is a multi-subunit enzyme that reads DNA and generates messenger RNA in the process known as transcription. Transcription, as the first step in gene expression, is tightly regulated by cyclin proteins and their associated kinases - cyclin dependent kinases (CDKs). Whilst the role of most CDKs in transcription regulation is well characterised, CDK12 and CDK13 have remained more elusive. Importantly, recent studies have suggested the dual inhibition of these kinases may provide a novel therapeutic strategy for a variety of cancers, in particular triple-negative breast cancer.
Here, Fan et al, use label free phosphoproteomics on IonOpticks Aurora series columns to identify substrates and overlap of CDK12 and CDK13, demonstrating significant redundancy between the two and identifying the key mechanism of anti-cancer efficacy during dual inhibition.
CDK13 cooperates with CDK12 to control global RNA polymerase II processivity
Science Advances. 29 Apr 2020: Vol. 6, no. 18. https://advances.sciencemag.org/content/6/18/eaaz5041
Fan Z, Devlin J, Hogg S, Doyle M, Harrison P, Todorovski I, Cluse L, Knight D, Sandow J, Gregory G, Fox A, Beilharz T, Kwiatkowski N, Scott N, Vidakovic A, Kelly G, Svejstrup J, Geyer M, Gray N, Vervoort S, Johnstone R