Bax conformational change is a crucial step for PUMA-mediated apoptosis in human leukemia

Biochem Biophys Res Commun. 2003 Oct 24;310(3):956-62. doi: 10.1016/j.bbrc.2003.09.109.


The BH3-only protein, PUMA, plays an important role in p53-mediated apoptosis. The apoptotic effect of PUMA on the mitochondria was studied using a p53-negative, human leukemia K562 cell line. Overexpression of PUMA was accompanied by an increased Bax expression, Bax conformational change, and translocation to mitochondria. A PUMA-BH3 peptide can induce Bax conformational change, cytochrome c release, and reduction in the mitochondrial membrane potential (DeltaPsi(m)) in isolated K562 mitochondria and can be inhibited by Bcl-XL. The homo-dimer of Bax/Bax was also weakly shown after mitochondria were treated with PUMA-BH3 peptide but may not be lethal for PUMA-induced apoptosis in K562 cells. Our results suggest that PUMA-induced Bax conformational change and Bax translocation to mitochondria can be separate events and the conformational change in Bax is crucial for PUMA-induced mitochondrial dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins
  • Apoptosis*
  • Blotting, Western
  • Cell Line, Tumor
  • Cross-Linking Reagents / pharmacology
  • Cytochromes c / metabolism
  • Cytosol / metabolism
  • Dimerization
  • Flow Cytometry
  • Humans
  • K562 Cells
  • Leukemia / metabolism*
  • Leukemia / pathology
  • Membrane Potentials
  • Mice
  • Mitochondria / metabolism
  • Peptides / chemistry
  • Protein Conformation
  • Protein Transport
  • Proteins / metabolism*
  • Proto-Oncogene Proteins / chemistry*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2*
  • Subcellular Fractions
  • Transfection
  • Tumor Suppressor Protein p53 / metabolism
  • bcl-2-Associated X Protein


  • Apoptosis Regulatory Proteins
  • BAX protein, human
  • BBC3 protein, human
  • Bax protein, mouse
  • Cross-Linking Reagents
  • Peptides
  • Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • Cytochromes c