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Updated: Jul 13, 2026

Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay
13:10

Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay

Published on: June 9, 2017

p73 is regulated by tyrosine kinase c-Abl in the apoptotic response to DNA damage

Z M Yuan1, H Shioya, T Ishiko

  • 1Department of Cancer Cell Biology, Harvard School of Public Health, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.

Nature
|July 3, 1999
PubMed

Insights

The tyrosine kinase c-Abl binds and phosphorylates the p73 protein, stimulating its role in apoptosis. This interaction is crucial for DNA damage-induced cell death, highlighting a new regulatory pathway for p73.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Oncology

Background:

  • p73 is a homologue of the p53 tumor suppressor but is not induced by DNA damage.
  • The tyrosine kinase c-Abl is activated by DNA damage and promotes apoptosis via p53-dependent and independent pathways.

Purpose of the Study:

  • To investigate the interaction between c-Abl and p73.
  • To determine if c-Abl regulates p73 activity in response to DNA damage.

Main Methods:

  • Co-immunoprecipitation to detect c-Abl/p73 binding in cells.
  • In vitro and in-cell phosphorylation assays using ionizing radiation.
  • Assays to measure p73-mediated transactivation and apoptosis.

Main Results:

  • c-Abl binds to p73 via its SH3 domain and the p73 carboxy-terminal domain.
  • c-Abl phosphorylates p73 at tyrosine 99 in response to ionizing radiation.
  • c-Abl enhances p73-mediated transactivation and apoptosis.
  • Disruption of the c-Abl-p73 interaction impairs ionizing-radiation-induced apoptosis.

Conclusions:

  • p73 is regulated by a c-Abl-dependent mechanism.
  • p73 plays a role in the apoptotic response to DNA damage.
  • The c-Abl-p73 interaction is critical for DNA damage-induced apoptosis.

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