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Transforming growth factor-beta stimulates p300-dependent RUNX3 acetylation, which inhibits ubiquitination-mediated

Yun-Hye Jin1, Eun-Joo Jeon, Qing-Lin Li

  • 1Department of Biochemistry and Urology, School of Medicine and Institute for Tumor Research, Chungbuk National University, Cheongju 361-763, South Korea.

The Journal of Biological Chemistry
|May 13, 2004
PubMed

Insights

RUNX3 protein levels are regulated by p300 acetylation, protecting it from degradation. This acetylation is influenced by TGF-beta signaling and histone deacetylase activity, revealing a new posttranslational control mechanism.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Runt domain transcription factors (RUNXs) are crucial for development and cancer.
  • RUNX1, RUNX2, and RUNX3 have distinct roles in hematopoiesis, osteogenesis, and cell development.
  • RUNX3 is implicated in T-cell and neuron development and gastric cancer genesis.

Purpose of the Study:

  • To investigate the posttranslational regulation of RUNX3.
  • To identify proteins that interact with and modify RUNX3.
  • To elucidate the role of acetylation in controlling RUNX3 protein stability.

Main Methods:

  • Co-immunoprecipitation assays to identify interacting proteins.
  • In vitro acetylation assays using p300 and RUNX3.
  • Western blotting to assess protein levels and degradation.
  • Analysis of signaling pathway involvement (TGF-beta, HDACs).

Main Results:

  • RUNX3 is identified as a direct target of p300 acetyltransferase activity.
  • Acetylation of three specific lysine residues in RUNX3 by p300 enhances its stability.
  • p300-mediated RUNX3 acetylation protects it from Smurf-mediated ubiquitination and degradation.
  • Transforming growth factor-beta signaling up-regulates RUNX3 acetylation, while histone deacetylase activity down-regulates it.

Conclusions:

  • RUNX3 protein stability is regulated by a balance of acetylation and deacetylation.
  • p300-mediated acetylation is a key mechanism for preventing RUNX3 degradation.
  • This competitive acetylation/deacetylation process provides a novel layer of posttranslational control over RUNX3 expression.

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