Bcl-2 prevents activation of CPP32 cysteine protease and cleavage of poly (ADP-ribose) polymerase and U1-70 kD proteins in staurosporine-mediated apoptosis
- PMID: 16465208
- DOI: 10.1038/sj.cdd.4400205
Bcl-2 prevents activation of CPP32 cysteine protease and cleavage of poly (ADP-ribose) polymerase and U1-70 kD proteins in staurosporine-mediated apoptosis
Abstract
Members of the the Bcl-2 and ICE/ced-3 gene families have been implicated as essential components in the control of the cell death pathway. Bcl-2 overexpression can prevent programmed cell death (PCD) in different cell types. ICE/ced-3-like proteases are synthesized as pro-enzymes and are activated by limited proteolysis. When overexpressed in diverse cell types, they trigger PCD. Bcl-2 can inhibit PCD mediated by these proteases, although as yet it is not clear at what specific step in the cell death pathway the protein acts. Here, we demonstrate that CPP32/Yama/Apopain, a member of the ICE/Ced-3 gene family, is processed during staurosporine-induced apoptosis in HeLa cells and that concomitant with CPP32 activation, two other proteins, poly (ADP-ribose) polymerase (PARP) and the U1-70 K small ribonucleoprotein, also undergo proteolysis. Overexpression of Bcl-2 prevents cleavage of CPP32, PARP and U1-70 K and protects HeLa cells from PCD. These results demonstrate that Bcl-2 controls PCD, by acting upstream of CPP32/Yama/Apopain.
Similar articles
-
Bcl-2 overexpression blocks activation of the death protease CPP32/Yama/apopain.Biochem Biophys Res Commun. 1996 Apr 16;221(2):340-5. doi: 10.1006/bbrc.1996.0597. Biochem Biophys Res Commun. 1996. PMID: 8619857
-
Baculovirus P35 inhibits the glucocorticoid-mediated pathway of cell death.Cancer Res. 1997 Jan 1;57(1):43-7. Cancer Res. 1997. PMID: 8988038
-
Zinc inhibits apoptosis upstream of ICE/CED-3 proteases rather than at the level of an endonuclease.Cell Death Differ. 1997 Feb;4(2):125-9. doi: 10.1038/sj.cdd.4400218. Cell Death Differ. 1997. PMID: 16465218
-
The apoptotic cysteine protease CPP32.Int J Biochem Cell Biol. 1997 Mar;29(3):393-6. doi: 10.1016/s1357-2725(96)00146-x. Int J Biochem Cell Biol. 1997. PMID: 9202418 Review.
-
Cold thoughts of death: the role of ICE proteases in neuronal cell death.Trends Neurosci. 1996 Dec;19(12):555-62. doi: 10.1016/s0166-2236(96)10067-9. Trends Neurosci. 1996. PMID: 8961485 Review.
Cited by
-
Bid induces the oligomerization and insertion of Bax into the outer mitochondrial membrane.Mol Cell Biol. 2000 Feb;20(3):929-35. doi: 10.1128/MCB.20.3.929-935.2000. Mol Cell Biol. 2000. PMID: 10629050 Free PMC article.
-
Role of Bcl-2 family members in caspase-independent apoptosis during Chlamydia infection.Infect Immun. 2002 Jan;70(1):55-61. doi: 10.1128/IAI.70.1.55-61.2002. Infect Immun. 2002. PMID: 11748163 Free PMC article.
-
Two CD95 (APO-1/Fas) signaling pathways.EMBO J. 1998 Mar 16;17(6):1675-87. doi: 10.1093/emboj/17.6.1675. EMBO J. 1998. PMID: 9501089 Free PMC article.
-
Reciprocal control of apoptosis and proliferation in cultured rat hepatoma arl-6 cells: roles of nutrient supply, serum, and oxidative stress.In Vitro Cell Dev Biol Anim. 2000 Jul-Aug;36(7):465-75. doi: 10.1290/1071-2690(2000)036<0465:RCOAAP>2.0.CO;2. In Vitro Cell Dev Biol Anim. 2000. PMID: 11039496
-
Bid-induced conformational change of Bax is responsible for mitochondrial cytochrome c release during apoptosis.J Cell Biol. 1999 Mar 8;144(5):891-901. doi: 10.1083/jcb.144.5.891. J Cell Biol. 1999. PMID: 10085289 Free PMC article.
LinkOut - more resources
Full Text Sources
Research Materials
