Bax-independent inhibition of apoptosis by Bcl-XL

Nature. 1996 Feb 8;379(6565):554-6. doi: 10.1038/379554a0.


The Bcl-2-related protein, Bcl-XL, has been shown to block apoptosis induced by a variety of stimuli and to be a stronger protector against apoptosis than Bcl-2 under certain circumstances. Using site-specific mutagenesis, we show here that the amino-acid residues critical for protection of cells by Bcl-XL against Sindbis virus-induced apoptosis are clustered within the Bcl-2-homology regions 1 and 2 (BH1 and BH2 regions). The residues necessary for Bcl-XL function are not identical to those required for Bcl-2 function. Although it has been suggested that heterodimerization between Bcl-XL and Bax is essential for the anti-death activity of Bcl-XL (refs 7,8), our results suggest that the interaction with Bax is not required for Bcl-XL to exert its death-repressing activity. Specific mutations that disrupt the ability of Bcl-XL to interact with Bax or Bak still preserve 70-80% of the anti-death activity of wild-type Bcl-XL.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Apoptosis / genetics
  • Apoptosis / physiology*
  • Binding Sites
  • Biopolymers
  • Cell Line
  • Genetic Vectors
  • Humans
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-bcl-2*
  • Sindbis Virus / physiology
  • Transfection
  • bcl-2-Associated X Protein
  • bcl-X Protein


  • BAX protein, human
  • BCL2L1 protein, human
  • Biopolymers
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • bcl-X Protein