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Updated: Feb 22, 2026

Examining BCL-2 Family Function with Large Unilamellar Vesicles
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Examining BCL-2 Family Function with Large Unilamellar Vesicles

Published on: October 5, 2012

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Extra-mitochondrial prosurvival BCL-2 proteins regulate gene transcription by inhibiting the SUFU tumour suppressor

Xiaofeng Wu1, Li-Shu Zhang1, Jason Toombs2,3

  • 1Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.

Nature Cell Biology
|September 26, 2017
PubMed

Insights

Anti-apoptotic BCL-2 proteins regulate cell survival by controlling gene expression, not just cell death. This discovery offers new strategies against cancer by targeting this novel BCL-2 protein function.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Cell Death Regulation

Background:

  • Pro- and anti-apoptotic BCL-2 family proteins interact at the outer mitochondrial membrane (OMM) to regulate apoptosis.
  • The canonical role of anti-apoptotic BCL-2 proteins is to prevent programmed cell death.

Purpose of the Study:

  • To investigate non-apoptotic functions of anti-apoptotic BCL-2 proteins.
  • To identify novel regulatory roles of BCL-2 proteins in cancer cell survival and growth.

Main Methods:

  • Investigated interactions between BCL-2 proteins and SUFU (suppressor of fused).
  • Assessed the impact of BCL-2 proteins on SUFU turnover and GLI transcriptional activity.
  • Analyzed the expression of GLI target genes, including BCL-2, MCL-1, and BCL-XL.

Main Results:

  • Three anti-apoptotic BCL-2 proteins (MCL-1, BCL-2, BCL-XL) function as transcriptional regulators.
  • These BCL-2 proteins bind to SUFU, promoting its turnover and inhibiting SUFU-GLI interactions.
  • BCL-2 proteins induce the expression of GLI target genes, creating a feedforward loop that enhances cancer cell survival.

Conclusions:

  • Anti-apoptotic BCL-2 proteins have a novel role in regulating prosurvival gene expression.
  • This BCL-2 protein/SUFU pathway promotes cancer cell survival and growth.
  • Targeting this pathway with BH3 mimetics offers a strategy against drug resistance in GLI-associated tumors.

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