Deep label free phosphoproteomics identifies novel mechanisms of kinase function.

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.

Read the full paper
CDK13 cooperates with CDK12 to control global RNA polymerase II processivity.
Science Advances. 29 Apr 2020: Vol. 6, no. 18.
doi: 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

Commentary by Andrew Webb, PhD.

About the author
Andrew has over 15 years’ experience in the field of chromatography and mass spectrometry. He is the lead innovator and inventor at IonOpticks, working closely with the team to test, refine and develop cutting edge techniques to support higher quality outputs and analytics from MS instruments. Andrew is also the Lab Head of the Walter and Eliza Hall Institute of Medical Research’s Proteomics Research Laboratory.