c-Myc transformation domain recruits the human STAGA complex and requires TRRAP and GCN5 acetylase activity for

Xiaohui Liu1, Jerusalem Tesfai, Yvonne A Evrard

  • 1Department of Biochemistry, University of California, Riverside 92521, USA.

Insights

The c-Myc oncoprotein (Myc) recruits the STAGA complex, including TRRAP and GCN5, to activate gene transcription in cancer. This interaction enhances cell proliferation and apoptosis control.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • Deregulation of c-Myc oncoprotein (Myc) is a key factor in numerous cancers.
  • Myc functions as a transcription factor controlling cell proliferation and apoptosis, but its mechanisms are not fully understood.
  • Myc's role in cell transformation involves interactions with TRRAP and GCN5, components of histone acetyltransferase (HAT) complexes.

Purpose of the Study:

  • To identify the specific HAT complexes recruited by Myc.
  • To elucidate the roles of TRRAP and GCN5 in Myc-mediated transcription activation.
  • To investigate the physical interactions between Myc, TRRAP, GCN5, and the STAGA complex.

Main Methods:

  • Investigated direct physical interactions between Myc's N-terminal domain and the STAGA coactivator complex.
  • Assessed the cooperative effects of GCN5 and TRRAP on Myc-induced transcription activation in vivo.
  • Determined the requirement of TRRAP's SPT3/GCN5 interaction domain and GCN5's HAT activity for synergistic transcription enhancement.

Main Results:

  • Myc directly co-recruits TRRAP and GCN5 through interactions with the human STAGA complex.
  • GCN5 and TRRAP synergistically enhance transcription activation mediated by Myc's N-terminal domain.
  • This synergistic effect is dependent on the SPT3/GCN5 interaction domain of TRRAP and the HAT activity of GCN5.

Conclusions:

  • Myc utilizes the STAGA complex, specifically TRRAP and GCN5, for transcriptional regulation.
  • TRRAP acts as an adaptor within STAGA, facilitating GCN5 HAT recruitment to Myc during transcription activation.
  • Understanding this mechanism provides insights into Myc's role in cancer and potential therapeutic targets.

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