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Updated: Jun 7, 2025

Identification of MyoD Interactome Using Tandem Affinity Purification Coupled to Mass Spectrometry
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Identification of MyoD Interactome Using Tandem Affinity Purification Coupled to Mass Spectrometry

Published on: May 17, 2016

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Myc 9aaTAD activation domain binds to mediator of transcription with superior high affinity

Andrea Knight1,2,3, Josef Houser4,5,6, Tomas Otasevic7

  • 1School of Life Science, Faculty of Science and Engineering, Anglia Ruskin University, East Road, Cambridge, CB1 1PT, UK. andrea.knight@aru.ac.uk.

Molecular Medicine (Cambridge, Mass.)
|November 13, 2024
PubMed

Insights

Targeting MYC genes in cancer is difficult. Researchers identified two key domains, acetyl-TAD and 9aaTAD, in c-Myc that work together for activation, offering a potential new therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • MYC gene overexpression is common in human cancers, including brain tumors.
  • MYC proteins are intrinsically disordered, making them challenging to target with drugs.
  • The nine-amino-acid activation domain (9aaTAD) is a key functional region in MYC proteins.

Purpose of the Study:

  • To identify and characterize functional domains within the c-Myc oncogene.
  • To investigate the interaction between c-Myc domains and coactivators.
  • To explore novel therapeutic strategies for MYC-driven cancers.

Main Methods:

  • Utilized a prediction algorithm to identify the 9aaTAD in c-Myc.
  • Performed transactivation assays to test the function of short c-Myc peptides.
  • Generated and tested c-Myc constructs with and without the 9aaTAD in a one-hybrid assay.
  • Characterized the acetyl-TAD domain and its collaboration with 9aaTAD.
  • Investigated interactions between Myc activation domains and the CBP coactivator's KIX domain using biophysical methods.

Main Results:

  • The 9aaTAD (region 100-108) was confirmed as a critical activation domain in c-Myc.
  • A novel collaborating domain, acetyl-TAD (region 69-103), was identified and characterized.
  • The presence of 9aaTAD strongly correlated with transcriptional activation.
  • Strong nanomolar interactions were observed between Myc-9aaTAD and the CBP KIX domain.
  • 9aaTADs were found to be conserved across the MYC family.

Conclusions:

  • The c-Myc oncogene's activation function is jointly mediated by the acetyl-TAD and 9aaTAD domains.
  • The interaction between c-Myc and the CBP KIX domain presents a druggable target for c-Myc-driven tumors.
  • Understanding these domains offers new avenues for developing targeted cancer therapies.
Keywords:
9aaTADCBPKIXMycMycN

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