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Publication : Differential requirement for caspase 9 in apoptotic pathways in vivo.

First Author  Hakem R Year  1998
Journal  Cell Volume  94
Issue  3 Pages  339-52
PubMed ID  9708736 Mgi Jnum  J:49087
Mgi Id  MGI:1276657 Doi  10.1016/s0092-8674(00)81477-4
Citation  Hakem R, et al. (1998) Differential requirement for caspase 9 in apoptotic pathways in vivo. Cell 94(3):339-52
abstractText  Mutation of Caspase 9 (Casp9) results in embryonic lethality and defective brain development associated with decreased apoptosis. Casp9-/- embryonic stem cells and embryonic fibroblasts are resistant to several apoptotic stimuli, including UV and gamma irradiation. Casp9-/- thymocytes are also resistant to dexamethasone- and gamma irradiation-induced apoptosis, but are surprisingly sensitive to apoptosis induced by UV irradiation or anti-CD95. Resistance to apoptosis is accompanied by retention of the mitochondrial membrane potential in mutant cells. In addition, cytochrome c is translocated to the cytosol of Casp9-/- ES cells upon UV stimulation, suggesting that Casp9 acts downstream of cytochrome c. Caspase processing is inhibited in Casp9-/- ES cells but not in thymocytes or splenocytes. Comparison of the requirement for Casp9 and Casp3 in different apoptotic settings indicates the existence of at least four different apoptotic pathways in mammalian cells.
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