Grant: Project Grant

The control of gene expression is key to all cellular processes. One universal player in this regulation is the Mediator complex. Mediator plays a central role in the regulation of gene expression acting as a bridge between the so-called general transcription factors (involved in the regulation of all genes) and the gene-specific transcription factors. Mediator is frequently mutated or present in abnormal level in many cancers and genetic diseases. Mediator contains a built-in regulator, an enzyme that adds phosphate groups on Mediator and other proteins, allowing for fine tuning its activity. This regulator module (called CKM) within Mediator is the most frequently Mediator component affected in cancers. Because it is an enzyme, the activity of CKM is in principle "drug-able" but before this can be achieved, a better understanding of how it works is required. In this project, we will use the power of budding yeast as a model system to dissect the mechanisms and function of CKM. This knowledge will leverage our capacity to mine strategies to re-equilibrate Mediator activity in diseases.