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Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
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Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c

Published on: June 29, 2011

ING1 induces apoptosis through direct effects at the mitochondria

P Bose1, S Thakur, S Thalappilly

  • 1Department of Biochemistry and Molecular Biology, Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada.

Cell Death & Disease
|September 7, 2013
PubMed

Insights

The ING1 tumor suppressor protein moves to mitochondria upon cellular stress, interacting with BAX to trigger apoptosis independently of p53. This reveals a new role for ING1 in programmed cell death.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • The ING family, including ING1, are tumor suppressors involved in epigenetic regulation, DNA repair, and apoptosis.
  • ING1 interacts with PCNA and 14-3-3 proteins, influencing its cellular localization and function.
  • Previous studies suggested ING1 affects apoptosis in a p53-dependent manner.

Purpose of the Study:

  • To investigate the role of ING1 in apoptosis induction and its subcellular localization.
  • To determine if ING1's mitochondrial translocation and apoptotic function are p53-dependent.
  • To elucidate the interaction of ING1 with other apoptotic regulators like BAX.

Main Methods:

  • Studied ING1 translocation to mitochondria in response to apoptosis-inducing stimuli in primary fibroblasts and epithelial cell lines.
  • Assessed the correlation between ING1 mitochondrial translocation and apoptosis induction in breast cancer cell lines after UV treatment.
  • Investigated endogenous ING1-BAX interaction and colocalization using biochemical and imaging techniques.
  • Utilized bioinformatics and sequence analysis to identify potential functional domains and interactions.

Main Results:

  • ING1 translocates to mitochondria in response to apoptotic stimuli, independent of p53 status.
  • ING1 directly interacts with and colocalizes with the pro-apoptotic protein BAX in a UV-inducible manner.
  • Mitochondria-targeted ING1 enhances apoptosis induction compared to wild-type ING1.
  • Bioinformatic analysis suggests interactions between yeast ING proteins and mitochondrial proteins, and ING1 possesses a BH3-like domain.

Conclusions:

  • Stress-induced ING1 relocalization to mitochondria, mediated by 14-3-3 proteins, promotes apoptosis through BAX interaction.
  • ING1 plays a direct role in regulating mitochondrial membrane permeability and apoptosis.
  • This study redefines the understanding of ING1's function in the cytoplasm and its contribution to programmed cell death.

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