TEThered to Runx: novel binding partners for runx factors

Xiaodong Li1, Matthew Decker, Jennifer J Westendorf

  • 1Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA.

Insights

RUNX2 interacts with FET/TET proteins, including FUS/TLS and EWSR1, influencing gene expression. These interactions may play roles in cancer development and cell differentiation.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • RUNX transcription factors are key regulators of gene expression, impacting development and disease.
  • Nuclear matrix proteins like RUNX2 integrate signaling pathways.
  • Previous studies identified Ddx5 and CoAA as Runx2 binding partners.

Purpose of the Study:

  • To identify novel Runx2 binding partners.
  • To investigate the interaction between Runx2 and FET/TET family proteins.
  • To explore the functional consequences of these interactions on transcriptional activity.

Main Methods:

  • Affinity purification and proteomic experiments were used to identify binding partners.
  • Co-immunoprecipitation assays confirmed interactions.
  • Reporter gene assays assessed transcriptional activity.

Main Results:

  • FUS/TLS, EWSR1, and the EWS-FLI fusion protein were identified as novel Runx2 binding partners.
  • The YxxQ motif, present in CoAA and FET/TET proteins, is crucial for Runx2 interaction.
  • Binding of FET/TET proteins to Runx2 altered its transcriptional activity.

Conclusions:

  • FET/TET proteins physically interact with Runx2.
  • These interactions can modulate Runx2-driven gene expression.
  • Protein complexes involving FET/TET and RUNX proteins may be implicated in tumorigenesis and progenitor cell differentiation.

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