Cyclin-dependent kinase 11 (CDK11) is a little studied, but essential protein that drives the growth of many cancers. CDK11 is believed to play a role in transcription and co-transcriptional mRNA-processing. However, its target genes and molecular functions are virtually unknown. Furthermore, studies of CDK11 have been hampered by the lack of specific chemical inhibitors to characterize its kinase activity, which will be very likely the key factor in the elucidation of the molecular mechanisms CDK11’s cellular function(s). Our recently published genome-wide data combined with biochemical experiments show that CDK11 specifically regulates transcription of 50 human histone genes (1). As histones are necessary for wrapping newly synthetized DNA into nucleosomes, this finding likely explains why fast-growing cancer cells are dependent on CDK11 activity. Moreover, the very recent study reported accidental finding of the very first candidate inhibitor of CDK11 among anti-cancer drugs with mischaracterized targets (2). Altogether, these findings create the very first opportunity for rational design and development of selective CDK11 inhibitors, which will serve as candidate anti-cancer compounds with high translational potential and facilitate functional studies of CDK11. This grant proposal is focused on the very first steps needed in this long-term research effort.

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Masaryk University is committed to the UN Sustainable Development Goals, which aim to improve the conditions and quality of life on our planet by 2030.

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