A brewing understanding of the regulation of Bax function by Bcl-xL and Bcl-2.
Bcl-2 family members form a network of protein-protein interactions that regulate apoptosis through permeabilization of the mitochondrial outer membrane. Deciphering this intricate network requires streamlined experimental models, including the heterologous expression in yeast. This approach had previously enabled researchers to identify domains and residues that underlie the conformational changes driving the translocation, the insertion and the oligomerization of the pro-apoptotic protein Bax at the level of the mitochondrial outer membrane. Recent studies that combine experiments in yeast and in mammalian cells have shown the unexpected effect of the anti-apoptotic protein Bcl-xL on the priming of Bax. As demonstrated with the BH3-mimetic molecule ABT-737, this property of Bcl-xL, and of Bcl-2, is crucial to elaborate about how apoptosis could be reactivated in tumoral cells.
Helmholtz Center for Infection Research, Junior Research Group Infection Biology of Salmonella, Inhoffenstraße 7, 38124 Braunschweig, Germany; Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.
Thibaud T
TT
Renault
California State University of Fresno, Department of Chemistry, 2555 E. San Ramon Ave M/S SB70, Fresno, CA 93740-8034, USA.
Laurent M
LM
Dejean
CNRS, UMR5095, 1 Rue Camille Saint-Saëns, 33077 Bordeaux, France; Université de Bordeaux, 146 Rue Léo Saignat, 33076 Bordeaux, France. Electronic address: manon@ibgc.cnrs.fr.
Stéphen
S
Manon
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D006801:Humans; D051336:Mitochondrial Membranes / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009596:Nitrophenols / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism*
C501332:ABT-737; C494826:BAX protein, human; C000595707:BCL2 protein, human; C494811:BCL2L1 protein, human; D001713:Biphenyl Compounds; D009596:Nitrophenols; D010879:Piperazines; D019253:Proto-Oncogene Proteins c-bcl-2; D013449:Sulfonamides; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
Apoptosis; Bax; Bcl-xL; Mitochondria; Yeast