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UV-induced binding of ING1 to PCNA regulates the induction of apoptosis

M Scott1, P Bonnefin, D Vieyra

  • 1Department of Biochemistry, Faculty of Medicine, The University of Calgary, 3330 Hospital Drive, NW, Calgary, Alberta T2N 4N1, Canada.

Journal of Cell Science
|October 30, 2001
PubMed

Insights

The ING1 protein (p33ING1b) binds to PCNA after UV exposure, influencing DNA repair and cell death pathways. This interaction is crucial for eliminating UV-damaged cells.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • p21(WAF1) binding to PCNA regulates DNA replication-repair switch.
  • The ING1 tumor suppressor gene is implicated in cellular responses to DNA damage.

Purpose of the Study:

  • To investigate the role of the p33(ING1b) isoform in UV-induced DNA repair and apoptosis.
  • To determine if p33(ING1b) interacts with PCNA and if this interaction is regulated by UV exposure.

Main Methods:

  • UV irradiation of cells
  • Co-immunoprecipitation assays to detect protein-protein interactions
  • Analysis of apoptosis induction in cells expressing wild-type and mutant ING1

Main Results:

  • UV rapidly induces p33(ING1b) to bind PCNA via its PIP domain.
  • This binding is competitive with p21(WAF1) and increases >10-fold after UV.
  • ING1 PIP mutants that fail to bind PCNA protect cells from UV-induced apoptosis.

Conclusions:

  • ING1 competitively binds PCNA, similar to other DNA damage and growth regulatory proteins.
  • The PCNA-ING1 interaction plays a role in eliminating UV-damaged cells through apoptosis.
  • ING1 may regulate the switch from DNA replication to repair by modulating the PCNA complex.

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