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Biochemical characterization of the feedforward loop between CDK1 and FOXM1 in epidermal stem cells
Maria Pia Polito1, Alessio Romaldini1, Lorenzo Tagliazucchi2
1Centre for Regenerative Medicine "Stefano Ferrari", Department of Life Science, University of Modena and Reggio Emilia, Via Glauco Gottardi 100, Modena, Italy.
Biology Direct
|October 13, 2024
Summary
Cyclin-dependent kinase 1 (CDK1) controls epidermal stem cell renewal by stabilizing FOXM1. This CDK1-FOXM1 feedforward loop is crucial for maintaining stem cells in human keratinocytes.
Area of Science:
- Stem cell biology
- Molecular cell biology
- Dermatology
Background:
- Self-renewal regulation in epidermal stem cells (EPSCs) is complex and not fully understood.
- FOXM1 is a key regulator, but its upstream activators are unknown.
Purpose of the Study:
- To identify the kinase regulating FOXM1 activity in human primary keratinocytes.
- To elucidate the molecular mechanisms controlling EPSC self-renewal.
Main Methods:
- Mass spectrometry to identify protein interaction networks.
- Biochemical assays to determine kinase activity and phosphorylation sites.
- Analysis of protein localization and transcriptional activity.
Main Results:
- CDK1 identified as the principal kinase phosphorylating FOXM1 in human keratinocytes.
- CDK1 stabilizes FOXM1, enhances its nuclear localization, and boosts transcriptional activity.
- FOXM1 positively regulates CDK1 expression, forming a feedforward loop.
- The CDK1-FOXM1 loop sustains EPSCs during in vitro culture.
Conclusions:
- The CDK1-FOXM1 feedforward loop is essential for maintaining epidermal stem cell self-renewal.
- Understanding FOXM1 regulation provides insights into keratinocyte stem cell mechanisms.
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