| Autor: |
Monney, Laurent, Otter, Isabelle, Olivier, Reynald, Ravn, Ulla, Mirzasaleh, Hengameh, Fellay, Isabelle, Poirier, Guy G., Borner, Christoph |
| Zdroj: |
Biochemical and Biophysical Research Communications; April 1996, Vol. 221 Issue: 2 p340-345, 6p |
| Abstrakt: |
TheC. elegansgene productced-9inhibits programmed cell death by negatively regulating the death-mediating proteaseced-3.The mammalian hormolog ofced-9is the oncoprotein Bcl-2. Overexpression of Bcl-2 spares mammalian and nematodal cells from dying and prevents ectopic cell death inced-9loss-of-function mutants. Although Bcl-2 has been shown to act as an antioxidant under certain conditions, additional functions have emerged from studies under low oxygen pressure. Here we show that Bcl-2 overexpression impairs activation of the interleukin-1β converting enzyme-related death protease CPP32/Yama/apopain, the mammalian homolog ofced-3.When U937 monocytes undergo programmed cell death in response to tumor necrosis factor α, the inactive CPP32 precursor is cleaved into its active forms. As a consequence poly(ADP ribose) polymerase, a major substrate of CPP32, is faithfully cleaved into a 85 kD fragment. Bcl-2 overexpressing cells are protected from tumor necrosis factor α-induced death and display neither CPP32 maturation nor PARP cleavage. The inhibitory effect of Bcl-2 on CPP32 activation is indirect since no physical interaction between the two proteins could be detected. These results indicate that Bcl-2 neutralizes an unknown cellular activator of CPP32 to save cells from programmed cell death. |
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