Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/9572
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Type: | Journal article |
Title: | Apaf-1 and caspase-9 accelerate apoptosis, but do not determine whether factor-deprived or drug-treated cells die |
Author: | Ekert, P. Read, S. Silke, J. Marsden, V. Kaufmann, H. Hawkins, C. Gerl, R. Kumar, S. Vaux, D. |
Citation: | The Journal of Cell Biology, 2004; 165(6):835-842 |
Publisher: | Rockefeller Univ Press |
Issue Date: | 2004 |
ISSN: | 0021-9525 1540-8140 |
Statement of Responsibility: | Paul G. Ekert, Stuart H. Read, John Silke, Vanessa S. Marsden, Hitto Kaufmann, Christine J. Hawkins, Robert Gerl, Sharad Kumar, and David L. Vaux |
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. |
Keywords: | apoptosis growth factor caspases Apaf-1 Bcl-2 |
DOI: | 10.1083/jcb.200312031 |
Published version: | http://dx.doi.org/10.1083/jcb.200312031 |
Appears in Collections: | Aurora harvest 4 Medicine publications |
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hdl_9572.pdf | 1.42 MB | Publisher's PDF | View/Open |
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