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Updated: May 15, 2026

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
11:36

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones

Published on: July 25, 2019

Domain-specific c-Myc ubiquitylation controls c-Myc transcriptional and apoptotic activity

Qin Zhang1, Erick Spears, David N Boone

  • 1Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232-2175, USA.

Proceedings of the National Academy of Sciences of the United States of America
|January 2, 2013
PubMed

Insights

The tumor suppressor ARF prevents c-Myc ubiquitylation, shifting its function from oncogenic to apoptotic. This switch activates Egr1, a key gene for c-Myc-induced apoptosis independent of p53.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Cellular Signaling

Background:

  • The transcription factor c-Myc drives cell growth but can also trigger cell death.
  • Tumor suppressors are required for c-Myc-induced apoptosis, but the underlying mechanisms remain unclear.

Purpose of the Study:

  • To elucidate the mechanism by which c-Myc transitions from an oncogenic to an apoptotic protein.
  • To investigate p53-independent apoptosis induced by c-Myc.

Main Methods:

  • Examined the role of ARF in mediating c-Myc-induced apoptosis.
  • Investigated the ubiquitylation of the c-Myc transcriptional domain (TD).
  • Assessed the interaction between ARF, c-Myc, and Skp2, and their effect on Egr1 promoter activity.

Main Results:

  • ARF inhibits TD ubiquitylation, crucial for c-Myc's oncogenic activity.
  • Inhibition of ubiquitylation promotes Egr1 expression, essential for p53-independent apoptosis.
  • ARF blocks c-Myc interaction with Skp2; Skp2 overexpression hinders ARF recruitment to the Egr1 promoter, inhibiting apoptosis.

Conclusions:

  • ARF is a critical mediator switching c-Myc's function from oncogenesis to apoptosis.
  • Targeting the ARF-Skp2-c-Myc axis offers potential therapeutic strategies for cancer.
  • Activating c-Myc's intrinsic apoptotic function could be a novel anti-tumorigenic approach.

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