Cleavage of Bax enhances its cell death function

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08:35

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Published on: October 5, 2012

D E Wood1, E W Newcomb

  • 1Department of Pathology, New York University School of Medicine and Kaplan Comprehensive Center, 550 First Avenue, New York, New York 10016, USA.

Experimental Cell Research
|April 25, 2000
PubMed

Insights

Cleavage of the proapoptotic protein Bax (p21) into its p18 form enhances its cell death-inducing activity. This p18 Bax form promotes apoptosis more potently than p21 Bax, independent of the mitochondrial permeability transition pore.

Area of Science:

  • Cellular biology
  • Molecular biology
  • Biochemistry

Background:

  • The Bcl-2 protein family regulates apoptosis.
  • Posttranslational modifications like cleavage alter protein function.
  • Caspases cleave proapoptotic and prosurvival Bcl-2 proteins, modulating their activity.

Purpose of the Study:

  • To investigate if the 18 kDa (p18) cleavage fragment of Bax exhibits increased cytotoxicity compared to the full-length 21 kDa (p21) form.
  • To determine the role of caspases and the mitochondrial permeability transition pore in Bax-mediated apoptosis.

Main Methods:

  • Transient transfection of human embryonic kidney 293T cells.
  • Analysis of cell death induction by p21 Bax and p18 Bax.
  • Assessment of apoptosis inhibition using pancaspase inhibitor Z-VAD-fmk and Cyclosporin A.

Main Results:

  • The p18 form of Bax demonstrated a more potent ability to induce cell death than p21 Bax.
  • Pancaspase inhibitor Z-VAD-fmk partially inhibited apoptosis induced by p18 Bax, but fully blocked apoptosis induced by p21 Bax.
  • Cyclosporin A had no effect on Bax-mediated apoptosis, indicating independence from the mitochondrial permeability transition pore.

Conclusions:

  • Cleavage of p21 Bax to the p18 form enhances its intrinsic cytotoxic properties.
  • The p18 form of Bax may augment its cell death function at the mitochondria.
  • Bax cleavage by calpain, rather than caspases, generates a more potent proapoptotic molecule.

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