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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
PubMed

Insights

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.
Keywords:
CDK1Epidermal stem cellFOXM1Phosphorylation

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