Arwa Alshanbari

• CDT Doctoral Researcher (Aligned) Supervisor: Prof Jane Endicott
• Email: a.m.h.alshanbari2@newcastle.ac.uk
• Project Title: Development of selective inhibitors of the cyclin K-SETD1A interaction as probes for its role in Acute Myeloid Leukaemia (AML).

Institution: Newcastle University

Project Summary: An interaction between cyclin K and the histone-lysine N-methyltransferase SETD1A is essential to the survival of acute myeloid leukaemia (AML) cells. This interaction, mediated by functional location on SETD1A (FLOS) domains of SETD1A, has been mapped to a site on cyclin K. Cyclin K, partnered with CDK12 or CDK13, regulates transcription elongation and termination steps by phosphorylating the C-terminal domain of RNA polymerase II, and also regulates mRNA splicing and translation. CDK12 has been described as both an oncoprotein and a tumour suppressor, suggesting regulation via its cyclin may impact its cellular effects. The aim of this project is to use structural, biophysical, synthetic chemistry and cell-based techniques to define the cyclin K-SETD1A interaction in molecular detail, toward modulating cyclin K (and thus CDK12) activity.