by on The Casein kinase 1 (CK1) family is a group of highly conserved protein kinases found across animals, fungi, plants, and protozoa. In humans, seven CK1 isoforms are known, each playing distinct yet sometimes overlapping roles in vital cellular processes. Despite their structural similarity, these kinases are involved in diverse functions and have been linked to several diseases, including Parkinson’s, Alzheimer’s, and various forms of cancer. As such, they represent promising targets for therapeutic intervention.
Our research focuses on the role of CK1 kinases in female cancer patients, specifically in relation to premature ovarian insufficiency (POI). Cancer treatments that damage DNA can unintentionally trigger oocyte cell death by activating the protein TAp63α, leading to infertility and long-term health issues such as osteoporosis and cardiovascular disease. CK1 kinases contribute to this process by phosphorylating and activating TAp63α. Modulating CK1 activity—without completely shutting it down—may offer a way to preserve fertility while maintaining the kinases’ essential roles, such as in circadian rhythm regulation.
To explore this therapeutic potential, we are using nuclear magnetic resonance (NMR) spectroscopy to study the residue-specific dynamics of isotope-labeled CK1δ. These experiments aim to identify flexible regions on the kinase surface that could be targeted by drugs to fine-tune CK1 activity. We are also investigating the structural and functional differences among CK1 family members to understand their individual contributions and selectively target only those involved in POI.
As a first step, we are using NMR with labeled peptides to compare how each CK1 isoform activates TAp63α in vitro. This approach reveals enzymatic distinctions between the family members. Additionally, we are working to optimize purification protocols for all CK1 isoforms—especially the less stable and poorly understood CK1α and CK1ε—to enable further structural and functional analysis.
Overall, our goal is to map the unique functions of each CK1 isoform and evaluate their potential as drug targets. By combining techniques such as NMR spectroscopy, X-ray crystallography, and cell-based assays, we aim to uncover the molecular mechanisms that differentiate CK1 kinases and open new pathways for targeted therapies—particularly those aimed at preventing POI in female cancer patients.
