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Updated: May 9, 2026

Examining BCL-2 Family Function with Large Unilamellar Vesicles
08:35

Examining BCL-2 Family Function with Large Unilamellar Vesicles

Published on: October 5, 2012

Conversion of Bcl-2 from protector to killer by interaction with nuclear orphan receptor Nur77/TR3

Bingzhen Lin1, Siva Kumar Kolluri, Feng Lin

  • 1The Burnham Institute, Cancer Center, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.

Cell
|February 26, 2004
PubMed

Insights

The Bcl-2 protein, a known apoptosis inhibitor, can promote cancer cell death by interacting with the Nur77 nuclear receptor. This interaction converts Bcl-2 into a cell-killer, offering new therapeutic strategies.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Bcl-2 family proteins are critical regulators of apoptosis.
  • Bcl-2 typically inhibits apoptosis but can promote cell death via an unknown mechanism.

Purpose of the Study:

  • To elucidate the mechanism by which Bcl-2 promotes cell death.
  • To investigate the interaction between Bcl-2 and orphan nuclear receptor Nur77 in cancer apoptosis.

Main Methods:

  • Co-immunoprecipitation to detect protein interactions.
  • Confocal microscopy for subcellular localization studies.
  • Analysis of apoptosis induction in cancer cells.

Main Results:

  • Bcl-2 directly interacts with orphan nuclear receptor Nur77 (TR3).
  • This interaction, mediated by Bcl-2's N-terminal loop, is essential for Nur77's mitochondrial localization and subsequent apoptosis.
  • Nur77 binding induces a conformational change in Bcl-2, exposing its BH3 domain and switching its function from protector to killer.

Conclusions:

  • Nur77 couples with the Bcl-2 apoptotic machinery.
  • Bcl-2 can exhibit opposing functions (protection vs. killing) based on interactions with proteins like Nur77.
  • These findings suggest novel strategies for cancer therapy by manipulating Bcl-2's apoptotic role.

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