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- Title
Apaf-1 and caspase-9 accelerate apotosis, but do not determine whether factor-deprived or durg-treated cells die.
- Authors
Ekert, Paul G.; Read, Stuart H.; Silke, John; Marsden, Vanessa S.; Kaufmann, Hitto; Hawkins, Christine J.; Gerl, Robert; Kumar, Sharad; Vaux, David L.
- Abstract
Apoptosis after growth factor withdrawal or drug treatment is associated with mitochondrial cytochrome c release and activation of Apaf-1 and caspase-9. To determine whether loss of Apaf-1, caspase-2, and caspase-9 prevented death of factor-starved cells, allowing them to proliferate when growth factor was returned, we generated IL-3-dependent myeloid lines from gene-deleted mice. Long after growth factor removal, cells lacking Apaf-1, caspase-9 or both caspase-9 and caspase-2 appeared healthy, retained intact plasma membranes, and did not expose phosphatidylserine. However, release of cytochrome c still occurred, and they failed to form clones when IL-3 was restored. Cells lacking caspase-2 alone had no survival advantage. Therefore, Apaf-1, caspase-2, and caspase-9 are not required for programmed cell death of factor-dependent cells, but merely affect its rate. In contrast, transfection with Bcl-2 provided long-term, clonogenic protection, and could act independently of the apoptosome. Unlike expression of Bcl-2, loss of Apaf-1, caspase-2, or caspase-9 would therefore be unlikely to enhance the survival of cancer cells.
- Subjects
APOPTOSIS; CELL death; MITOCHONDRIA; ORGANELLES; GROWTH factors; CYTOCHROMES
- Publication
Journal of Cell Biology, 2004, Vol 165, Issue 6, p835
- ISSN
0021-9525
- Publication type
Article
- DOI
10.1083/jcb.200312031