Bcl-XL and Bcl-2 repress a common pathway of cell death.
The effect of Bcl-xL upon the developmental death of T cells was assessed by generating transgenic mice that expressed Bcl-xL within all thymocyte subsets. Bcl-xL protected thymocytes from a variety of apoptotic stimuli, including gamma irradiation, glucocorticoids, and anti-CD3 treatment. Bcl-xL altered thymocyte maturation, resulting in increased numbers of CD3int/hi and CD4-8+ thymocytes. Overall, the phenotype of Bcl-xL transgenics was essentially indistinguishable from a Bcl-2 transgenic model. Overexpression of Bcl-xL or Bcl-2 resulted in the down-regulation of the other molecule, providing further evidence of their reciprocal regulation. In a genetic test of redundancy, the Bcl-xL transgene rescued mature T cells in Bcl-2 null mice. Immunoprecipitation indicated that Bcl-xL, like Bcl-2, heterodimerized with the death-promoting molecule Bax in thymocytes. This in vivo model argues that Bcl-xL, like Bcl-2, functions in a common pathway to repress cell death.
Chao
D T
DT
Howard Hughes Medical Institute, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Linette
G P
GP
Boise
L H
LH
White
L S
LS
Thompson
C B
CB
Korsmeyer
S J
SJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D017252:CD3 Complex / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology; D005720:Gamma Rays; D005816:Genetic Complementation Test; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D046911:Macromolecular Substances; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D000911:Antibodies, Monoclonal; C494827:Bax protein, mouse; C494812:Bcl2l1 protein, mouse; D017252:CD3 Complex; D046911:Macromolecular Substances; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D003907:Dexamethasone; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)