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Cancer

RUNX2 Plays a Critical Role in Cancer Cell Response to DNA Damage

Strategic Insights

— 1 min read

Cancer cells have been found to modify their nuclear architecture and transcriptional control, which enables them to grow and metastasize. Research at Mayo Clinic has identified RUNX family transcriptional scaffolding proteins as key factors in this process. Proteomic analysis revealed that RUNX2 interacts with three distinct proteins that respond to DNA damage, forming UV-responsive complexes with the serine-139-phosphorylated isoform of H2AX (cH2AX). The interaction of RUNX2 with these proteins plays a critical role in the cancer cells' ability to respond to DNA damage.

Key Takeaways:

  • RUNX2 is a transcriptional scaffolding protein that plays a critical role in cancer cell response to DNA damage.
  • RUNX2 interacts with three distinct proteins that respond to DNA damage, including RUVBL2, INTS3, and BAZ1B.
  • These interactions form UV-responsive complexes with the serine-139-phosphorylated isoform of H2AX (cH2AX).
  • The interaction of RUNX2 with BAZ1B and cH2AX decreases histone H3 lysine 9 acetylation levels, marking accessible chromatin for repair.
  • RUNX2 depletion prevents the BAZ1B-cH2AX interaction and attenuates loss of H3K9 and H3K56 acetylation.
  • The data suggest a cytoprotective function for RUNX2 in cancer cells, which may clarify its expression in chemotherapy-resistant and/or metastatic tumors.
  • Research at Mayo Clinic identified RUNX2-dependent protein-protein interactions associated with the nuclear matrix in bone, breast, and prostate tumor cell types.
  • The study found that RUNX2 interacts with RUVBL2, INTS3, and BAZ1B, forming UV-responsive complexes with cH2AX.

Statistics:

  • 3 distinct proteins interact with RUNX2 in response to DNA damage: RUVBL2, INTS3, and BAZ1B.
  • 1 UV-responsive complex formed with cH2AX (serine-139-phosphorylated isoform of H2AX) is associated with RUNX2.
  • 2 histone modifications (H3K9 and H3K56 acetylation) are decreased following RUNX2 depletion.
  • 1 chromosome function is affected by RUNX2-interactions with BAZ1B and cH2AX.

Sources:

  • Subnuclear domain proteins in cancer cells support the functions of RUNX2 in the DNA damage response. Journal of Cell Science, 2015;128(4):728-740.
  • Company Of Biologists Ltd, Bidder Building Cambridge Commercial Park Cowley Rd, Cambridge CB4 4DL, Cambs, England.

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