Bcl-2 Overexpression Blocks Activation of the Death Protease CPP32/Yama/Apopain

Monney, Laurent; Otter, Isabelle; Ravn, Ulla; Mirzasaleh, Hengameh; Fellay, Isabelle; Poirier, Guy G.; Borner, Christoph

doi:10.1006/bbrc.1996.0597

Cited by 64 publications

(42 citation statements)

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“…Regarding the site of action of Bcl-2 in the GCinduced death pathway, the observed inhibition of PARP cleavage and DEVDase activity by Bcl-2 up to 48 h is in good agreement with numerous reports placing Bcl-2 upstream of the activation of at least some`eector' caspases (Boulakia et al, 1996;Chinnaiyan et al, 1996;Monney et al, 1996;Messmer et al, 1996;Smyth et al, 1996;Shimizu et al, 1996;Armstrong et al, 1996;Melkova et al, 1997;Mandal et al, 1996;Ibrado et al, 1996;Brunet et al, 1998;Adelman et al, 1983;Morimoto and Schlossman, 1985). By mechanisms brie¯y outlined in the Introduction, Bcl-2 may prevent a putative GC-induced death signal to release caspase activating factors from the mitochondria, thereby initiating the terminal`common' eector phase of the death pathway.…”

Section: Discussionsupporting

confidence: 90%

“…As exempli®ed in Figure 3a, withdrawal of doxycycline (i.e., induction of exogenous Bcl-2) prevented cleavage of the 113 kD PARP molecule into the 89 kD fragment typical for GCinduced apoptosis (Geley et al, 1997b;Robertson et al, 1997). Thus, in this human leukemia model, like in many other systems (Boulakia et al, 1996;Chinnaiyan et al, 1996;Monney et al, 1996;Messmer et al, 1996;Smyth et al, 1996;Shimizu et al, 1996;Armstrong et al, 1996;Melkova et al, 1997;Mandal et al, 1996;Ibrado et al, 1996), Bcl-2 acted upstream of caspasemediated PARP cleavage. However, when the exogenous Bcl-2 expressing cell lines were cultured in the continuous presence of GC for longer periods (which leads to apoptosis, see Figure 2), PARP cleavage was observed (Figure 3a).…”

Section: Cem-c7h2supporting

confidence: 51%

“…Subsequently, Bcl-2 has been shown to be the prototype of a structurally related family of apoptosis-promoting and -preventing proteins whose balance might be critical for cell survival (Oltvai and Korsmeyer, 1994;Cory, 1995). Bcl-2 prevents caspase activation and apoptosis in several (Boulakia et al, 1996;Chinnaiyan et al, 1996;Monney et al, 1996;Messmer et al, 1996;Smyth et al, 1996;Shimizu et al, 1996;Armstrong et al, 1996;Melkova et al, 1997;Mandal et al, 1996;Ibrado et al, 1996;Brunet et al, 1998), although not all (Chinnaiyan et al, 1996;, systems. Since Bcl-2 and its antagonist Bax are potential pore-forming proteins (Minn et al, 1997;Schendel et al, 1997;Antonsson et al, 1997), Bcl-2 might interfere with the mitochondrial release of APAF-2 (apoptosis protease-activating factor 2)/cytochrome c (Kluck et al, 1997;Yang et al, 1997;Kharbanda et al, 1997) and/or other apoptosis-inducing factors (Susin et al, 1996;Decaudin et al, 1997), that may trigger the caspase cascade.…”

Section: Introductionmentioning

confidence: 99%

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Bcl-2 interferes with the execution phase, but not upstream events, in glucocorticoid-induced leukemia apoptosis

et al. 1999

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Section: Discussionsupporting

confidence: 90%

Section: Cem-c7h2supporting

confidence: 51%

Section: Introductionmentioning

confidence: 99%

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Bcl-2 interferes with the execution phase, but not upstream events, in glucocorticoid-induced leukemia apoptosis

et al. 1999

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“…Bcl-2, the processing of downstream caspases including caswhich can interact with FADD and thereby activate the proximal caspase pase-3 is prevented by Bcl-2 or Bcl-xL in many apoptotic sys-cascade. tems [248,249]. Thus, Bcl-2 proteins may inhibit cell death by acting downstream of initiator but upstream of executioner caspases.…”

Section: Flice-inhibitory Proteinsmentioning

confidence: 99%

Apoptosis signaling by death receptors

Schulze‐Osthoff

Ferrari

Łos

et al. 1998

European Journal of Biochemistry

888

576

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Death receptors have been recently identified as a subgroup of the TNF-receptor superfamily with a predominant function in induction of apoptosis. The receptors are characterized by an intracellular region, called the death domain, which is required for the transmission of the cytotoxic signal. Currently, five different such death receptors are known including tumor necrosis factor (TNF) receptor-1, CD95 (Fas/ APO-1), TNF-receptor-related apoptosis-mediated protein (TRAMP) and TNF-related apoptosis-inducing ligand (TRAIL) receptor-1 and -2. The signaling pathways by which these receptors induce apoptosis are rather similar. Ligand binding induces receptor oligomerization, followed by the recruitment of an adaptor protein to the death domain through homophilic interaction. The adaptor protein then binds a proximal caspase, thereby connecting receptor signaling to the apoptotic effector machinery. In addition, further pathways have been linked to death receptor-mediated apoptosis, such as sphingomyelinases, JNK kinases and oxidative stress. These pro-apoptotic signals are counteracted by several mechanisms which inhibit apoptosis at different levels. This review summarizes the current and rapidly expanding knowledge about the biological functions of death receptors and the mechanisms to trigger or to counteract cell death.Keywords : apoptosis; Bcl-2; caspase; CD95 (APO-1/Fas) ; death receptor; inhibitor of apoptosis protein; nuclear factor-κB ; tumor-necrosis factor; tumor-necrosis-factor-related apoptosis-inducing ligand; tumornecrosis-factor-receptor-related apoptosis-mediating protein.Apoptosis or programmed cell death is the innate mechanism modelling, immune regulation and tumor regression. Cells undergoing apoptosis show a sequence of cardinal morphological by which the organism eliminates unwanted cells. In contrast to necrosis, apoptosis is the most common physiological form of features including membrane blebbing, cellular shrinkage and condensation of chromatin. Biochemically, these alterations are cell death and occurs during embryonic development, tissue reassociated with the translocation of phosphatidylserine to the duced following traumatic injury or exposure to high concentra-

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“…With the goal of identifying the mechanism of cell death regulation, eorts have been made to de®ne the molecular order of the function of the Bcl-2 family and the caspase family. Earlier studies revealed that Bcl-2 can inhibit the apoptosis induced by active caspases (Martin et al, 1995;Enari et al, 1995), while more recent studies demonstrated that Bcl-2 and other antiapoptotic Bcl-2 family members, Bcl-x L and adenovirus E1B 19K, suppress apoptosis by inhibiting processing and activation of caspases (Armstrong et al, 1996;Boulakia et al, 1996;Chinnaiyan et al, 1996;Cosulich et al, 1996;Erhardt and Cooper, 1996;Ibrado et al, 1996;Jacobson et al, 1996;Monney et al, 1996;Shimizu et al, 1996;Perry et al, 1997;Estoppey et al, 1997). Although many studies have investigated antiapoptotic Bcl-2 family members, studies examining the step at which proapoptotic Bcl-2 family members function in the apoptotic signaling pathway are apparently lacking.…”

Section: Introductionmentioning

confidence: 99%

Caspase-dependent apoptosis of COS-7 cells induced by Bax overexpression: differential effects of Bcl-2 and Bcl-xL on Bax-induced caspase activation and apoptosis

et al. 1997

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Bcl-2 family proteins and ICE/CED-3 family proteases (caspases) are regarded as the basic regulators of apoptotic cell death. They are evolutionarily conserved and implicated in a variety of apoptosis. However, the precise mechanism by which these two families interact to regulate cell death is not yet known. In this study, we found that the overexpression of the Bcl-2 family member Bax induced apoptotic cell death in COS-7 cells through the activation of CPP32 (caspase-3)-like proteases that cleaved the DEVD tetrapeptide. This apoptotic cell death was suppressed by the viral proteins CrmA and p35, as well as by the chemically synthesized caspase inhibitors Z-Asp-CH 2 -DCB and zVAD-fmk. We also found that the Bax-induced apoptosis of COS-7 cells was suppressed by Bcl-x L and Bcl-2, though both Bcl-x L and Bcl-2 similarly prevented etoposide-induced apoptosis in COS-7 cells. In addition, Bcl-x L inhibited the activation of caspase-3-like proteases accompanying Bax-induced COS-7 cell death but Bcl-2 did not. These results indicate that the caspase activation is essential for Bax-induced apoptosis, and that the ability of Bcl-2 and Bcl-x L to prevent the Bax-induced caspase activation and apoptosis in COS-7 cells could be dierentially regulated. Our results also suggest that Bcl-2 family proteins function upstream of caspase activation and control apoptosis through the regulation of caspase activity.

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Bcl-2 Overexpression Blocks Activation of the Death Protease CPP32/Yama/Apopain

Cited by 64 publications

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Bcl-2 interferes with the execution phase, but not upstream events, in glucocorticoid-induced leukemia apoptosis

Bcl-2 interferes with the execution phase, but not upstream events, in glucocorticoid-induced leukemia apoptosis

Apoptosis signaling by death receptors

Caspase-dependent apoptosis of COS-7 cells induced by Bax overexpression: differential effects of Bcl-2 and Bcl-xL on Bax-induced caspase activation and apoptosis

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