Publications by authors named "S Korsmeyer"
Most intrinsic death signals converge into the activation of pro-apoptotic BCL-2 family members BAX and BAK at the mitochondria, resulting in the release of cytochrome c and apoptosome activation. Chronic endoplasmic reticulum (ER) stress leads to apoptosis through the upregulation of a subset of pro-apoptotic BH3-only proteins, activating BAX and BAK at the mitochondria. Here we provide evidence indicating that the full resistance of BAX and BAK double deficient (DKO) cells to ER stress is reverted by stimulation in combination with mild serum withdrawal.
View Article and Find Full Text PDFExercise has beneficial effects on human health, including protection against metabolic disorders such as diabetes. However, the cellular mechanisms underlying these effects are incompletely understood. The lysosomal degradation pathway, autophagy, is an intracellular recycling system that functions during basal conditions in organelle and protein quality control.
View Article and Find Full Text PDFThe threonine endopeptidase Taspase1 has a critical role in cancer cell proliferation and apoptosis. In this study, we developed and evaluated small molecule inhibitors of Taspase1 as a new candidate class of therapeutic modalities. Genetic deletion of Taspase1 in the mouse produced no overt deficiencies, suggesting the possibility of a wide therapeutic index for use of Taspase1 inhibitors in cancers.
View Article and Find Full Text PDFArticle Synopsis
- Acute exposure to ionizing radiation can lead to a lethal condition in the gastrointestinal tract known as GI syndrome, raising questions about how and which cells are affected.
- Research on mouse models revealed that deleting key pro-apoptotic genes (Bak1 and Bax) from GI epithelial or endothelial cells does not prevent the development of GI syndrome after radiation exposure.
- However, removing the p53 gene from GI epithelial cells made the mice more susceptible to GI syndrome, while mice with high levels of p53 were protected, indicating that the death of GI epithelial cells plays a critical role in the condition, and this process involves p53 but is not solely due to apoptosis.