Apaf-1 and caspase-9 accelerate apoptosis, but do not determine whether factor-deprived or drug-treated cells die

Ekert, PG; Read, SH; Silke, J; Marsden, VS; Kaufmann, H; Hawkins, CJ; Gerl, R; Kumar, S; Vaux, DL

Author(s): Ekert, PG; Read, SH; Silke, J; Marsden, VS; Kaufmann, H; Hawkins, CJ; Gerl, R; Kumar, S; Vaux, DL;
Details: Publication Year 2004-06-21,Volume 165,Issue #6,Page 835-842
Journal Title: JOURNAL OF CELL BIOLOGY
Publication Type: Journal Article
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.
Publisher: ROCKEFELLER UNIV PRESS
Keywords: BCL-2 GENE; B-CELLS; DEATH; CED-4; ACTIVATION; SURVIVAL; PATHWAYS; MYC; REQUIREMENT; INHIBITION
Publisher's Version: https://doi.org/10.1083/jcb.200312031
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2004-06-21 12:00:00