Prosurvival Bcl-2 family members affect autophagy only indirectly, by inhibiting Bax and Bak
Copyright policy )Prosurvival Bcl-2 family members affect autophagy only indirectly, by inhibiting Bax and Bak
Significance It is widely accepted that prosurvival B-cell lymphoma 2 (Bcl-2) family members not only inhibit apoptosis but also negatively regulate autophagy by binding to Beclin 1. Herein, we challenge this view and provide genetic and biochemical evidence that the effects of prosurvival Bcl-2 family members on autophagy are instead an indirect consequence of their inhibition of apoptosis mediators Bcl-2–associated X (Bax) and Bcl-2 homologous antagonist/killer (Bak). We show that in the absence of Bax and Bak, antagonizing or altering the levels of prosurvival Bcl-2 family members has no detectable impact on autophagy. Because several inhibitors of both autophagy and Bcl-2 are in clinical trials for the treatment of cancer, it is important to understand the cross-talk between these pathways.
- Walter and Eliza Hall Institute of Medical Research Australia
- University of Melbourne Australia
Mice, Knockout, Cell Survival, Biphenyl Compounds, Blotting, Western, Apoptosis, Fibroblasts, Embryo, Mammalian, Flow Cytometry, Piperazines, Autophagy-Related Protein 5, Nitrophenols, Mice, Proto-Oncogene Proteins c-bcl-2, Phagosomes, Autophagy, Animals, Myeloid Cell Leukemia Sequence 1 Protein, Microtubule-Associated Proteins, Cells, Cultured, Cell Line, Transformed
Mice, Knockout, Cell Survival, Biphenyl Compounds, Blotting, Western, Apoptosis, Fibroblasts, Embryo, Mammalian, Flow Cytometry, Piperazines, Autophagy-Related Protein 5, Nitrophenols, Mice, Proto-Oncogene Proteins c-bcl-2, Phagosomes, Autophagy, Animals, Myeloid Cell Leukemia Sequence 1 Protein, Microtubule-Associated Proteins, Cells, Cultured, Cell Line, Transformed
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).173 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
Citations provided by BIP!Popularity provided by BIP!