Back to Search
Start Over
Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes
Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes
- Source :
- Genes & Development. 12:806-819
- Publication Year :
- 1998
- Publisher :
- Cold Spring Harbor Laboratory, 1998.
-
Abstract
- Caspases are fundamental components of the mammalian apoptotic machinery, but the precise contribution of individual caspases is controversial. CPP32 (caspase 3) is a prototypical caspase that becomes activated during apoptosis. In this study, we took a comprehensive approach to examining the role of CPP32 in apoptosis using mice, embryonic stem (ES) cells, and mouse embryonic fibroblasts (MEFs) deficient for CPP32. CPP32(ex3-/-) mice have reduced viability and, consistent with an earlier report, display defective neuronal apoptosis and neurological defects. Inactivation of CPP32 dramatically reduces apoptosis in diverse settings, including activation-induced cell death (AICD) of peripheral T cells, as well as chemotherapy-induced apoptosis of oncogenically transformed CPP32(-/-) MEFs. As well, the requirement for CPP32 can be remarkably stimulus-dependent: In ES cells, CPP32 is necessary for efficient apoptosis following UV- but not gamma-irradiation. Conversely, the same stimulus can show a tissue-specific dependence on CPP32: Hence, TNFalpha treatment induces normal levels of apoptosis in CPP32 deficient thymocytes, but defective apoptosis in oncogenically transformed MEFs. Finally, in some settings, CPP32 is required for certain apoptotic events but not others: Select CPP32(ex3-/-) cell types undergoing cell death are incapable of chromatin condensation and DNA degradation, but display other hallmarks of apoptosis. Together, these results indicate that CPP32 is an essential component in apoptotic events that is remarkably system- and stimulus-dependent. Consequently, drugs that inhibit CPP32 may preferentially disrupt specific forms of cell death.
- Subjects :
- Cytotoxicity, Immunologic
Male
Programmed cell death
CD3 Complex
Neutrophils
Ultraviolet Rays
T-Lymphocytes
Longevity
Gene Expression
Apoptosis
Bone Marrow Cells
Mice, Inbred Strains
Caspase 3
Embryonic and Fetal Development
Mice
Osmotic Pressure
Tumor Cells, Cultured
Genetics
Animals
fas Receptor
Caspase
Cell Nucleus
B-Lymphocytes
Cell Death
biology
Stem Cells
Intrinsic apoptosis
Embryo, Mammalian
Embryonic stem cell
Mice, Mutant Strains
Cell biology
Mice, Inbred C57BL
Cysteine Endopeptidases
UVB-induced apoptosis
Caspases
Mutation
biology.protein
Female
Stem cell
Cell Division
Research Paper
Developmental Biology
Subjects
Details
- ISSN :
- 08909369
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Genes & Development
- Accession number :
- edsair.doi.dedup.....923ee55fa2697cce78f49e8be3685abf
- Full Text :
- https://doi.org/10.1101/gad.12.6.806