Fas-induced Activation of the Cell Death-related Protease CPP32 Is Inhibited by Bcl-2 and by ICE Family Protease Inhibitors

Armstrong, Robert C.; Aja, Teresa; Xiang, Jialing; Gaur, Smita; Krebs, Joseph F.; Hoang, Kim; Bai, Xu; Korsmeyer, Stanley J.; Karanewsky, Donald S.; Fritz, Lawrence C.; Tomaselli, Kevin J.

doi:10.1074/jbc.271.28.16850

Cited by 293 publications

(228 citation statements)

References 46 publications

(68 reference statements)

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“…The induction of DEVDase activity, DNA fragmentation, and externalization of phosphatidylserine in response to RRM treatment was completely abolished in all clones overexpressing Bcl-2 or Bcl-X L (Figure 3b,c and data not shown). In agreement with previously reported data, 56,57 Bcl-2 as well as Bcl-X L also inhibited the induction of apoptosis mediated by Fas signals (Figure 3b,c). The inhibition of DEVDase activity and DNA fragmentation by Bcl-2 was observed even after 24 h of incubation with the RRMs (data not shown).…”

Section: Expression Of Bcl-2 and Bcl-x L In Jurkat Cells Prevents Rrmsupporting

confidence: 93%

Retinoid-related molecules require caspase 9 for the effective release of Smac and the rapid induction of apoptosis

López-Hernández¹,

Ortiz²,

Bayón³

et al. 2003

Cell Death Differ

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Certain retinoid-related molecules (RRMs) with agonist or antagonist activities have been described to induce apoptosis in a variety of cancer cell lines and show promise for the treatment of cancer. Similar to other chemotherapeutic drugs, these retinoid analogs have been suggested to induce apoptosis through the intrinsic pathway, which requires the release of cytochrome c from the mitochondria for the effective activation of caspase 9. Expression of a catalytically inactive form of caspase 9, which functions as a dominant negative mutant, inhibits the induction of DEVDase activity and nuclear fragmentation by selective RRMs. Whereas the RRMs could induce the release of cytochrome c in the absence of caspase 9 activity, the later is necessary for the effective release of Smac/Diablo from the mitochondria. Furthermore, overexpression of Bcl-2 or Bcl-X L also inhibits RRM-induced apoptosis. We demonstrate that activation of caspase 2 by the agonist MX2870-1 requires caspase 9 activity and is inhibited by Bcl-2 overexpression. In contrast, the antagonist MX781 induces cleavage of procaspase 2 upstream of mitochondria and independently of caspase 9. Thus, two retinoid analogs with unique characteristics activate two distinct apical caspases (2 or 9) to initiate apoptosis. In addition to caspase-mediated cell death, sustained exposure to the RRMs can also lead to loss of cell viability in cells lacking caspase 9 activity or in cells stimulated in the presence of the caspase inhibitor Z-VADfmk. Moreover, MX2870-1 and MX781 produce cell cycle arrest independently of caspase activity and the retinoid receptors.

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Section: Expression Of Bcl-2 and Bcl-x L In Jurkat Cells Prevents Rrmsupporting

confidence: 93%

Retinoid-related molecules require caspase 9 for the effective release of Smac and the rapid induction of apoptosis

López-Hernández¹,

Ortiz²,

Bayón³

et al. 2003

Cell Death Differ

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“…Jurkat T cell clones stably transfected with the human bcl-2 gene (bcl-2) or control vector (neo) were kindly provided by S. Korsmeyer (Dana Farber Cancer Institute, Boston, MA) and cultured exactly as described [31]. Cells were grown in RPMI 1640 medium supplemented with 10% fetal calf serum.…”

Section: Methodsmentioning

confidence: 99%

Differential Effects of Bcl-2 on Cell Death Triggered under ATP-Depleting Conditions

Single

Leist

Nicotera

2001

Experimental Cell Research

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The intracellular ATP concentration decides on the onset of either apoptosis or necrosis in Jurkat cells exposed to death stimuli. Bcl-2 can block apoptotic demise, which occurs preferably under conditions of high cellular ATP levels. Here, we investigated the effects of Bcl-2 on the necrotic type of cell demise that prevails under conditions of energy loss. ATP levels were modulated by using mitochondrial inhibitors, such as rotenone or S-nitrosoglutathione, in medium either lacking glucose or supplemented with glucose to stimulate glycolytic ATP generation. Under conditions of ATP depletion, staurosporine (STS) induced >90% necrosis in vector control-transfected cells, whereas bcl-2-transfected cells were protected. Thus, the antiapoptotic protein Bcl-2 can reduce the overall amount of cell death in ATP-depleted cells regardless whether it occurs by apoptosis or necrosis. Cytochrome c release, normally preceding STS-induced necrosis, was also inhibited by Bcl-2. However, Bcl-2 did not prevent an initial STS-induced drop of the mitochondrial membrane potential (⌬⌿ m ). Therefore, the mechanisms whereby Bcl-2 prevents cell death and favors retention of cytochrome c in the mitochondria require neither the maintenance of mitochondrial ⌬⌿ nor the maintenance of normal ATP levels.

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“…To quantify the kinetic changes of caspase-3 more precisely, the enzyme activity in cell extracts of GCV-treated B16F10/TK-C19 and 1MEA 7R.1/TK-C1 cells was measured by using a chromogenic tetrapeptide substrate, Asp-Glu-Val-Asp-pNA (Ac-DEVD-pNA), with or without the addition of a specific inhibitor, Ac-DEVD-CHO, or Tyr-Val-Ala-Asp-CHO (Ac-YVAD-CHO) that can specifically inhibits caspase-1 (ICE-like enzyme) but not caspase-3. 19 As shown in Table 1, the peak of caspase-3 activity in GCV-treated B16F10/TK-C19 melanoma cells occurred at 48-60 h, confirming the immunoblot results, while the peak activity in GCV-treated 1MEA 7R.1/TK-C1 hepatoma cells was detected at 24-48 h. The results clearly indicate that indeed the activation of caspase-3, as well as apoptosis, kinetically followed the induction of FasL protein in the HSVtk-transduced GCV-treated tumor cells.…”

Section: Downstream Apoptosis Regulators/effectors and Cysteine Protementioning

confidence: 99%

“…With the findings of 'death domain'-containing proteins such as RIP, 15 elucidation of functional roles of interleukin-1␤-converting enzyme (ICE/caspase-1) and related cysteine protease, particularly caspase-3, [16][17][18][19] and demonstration of poly(ADP-ribose) polymerase (PARP) 18 as a substrate for caspase-3, schemata of major pathways of apoptosis have been postulated. 14 The results of our kinetic analysis ( Figure 5 and Table 1) would support that RIP and caspase-3 play key roles in the Fas/FasL apoptosis pathway of these murine tumors, although the possible participation of PARP remains to be clarified.…”

Section: Figure 6 Involvement Of Fasl In Hsvtk/gcv-induced Apoptosismentioning

confidence: 99%

Involvement of Fas (CD95/APO-1) and Fas ligand in apoptosis induced by ganciclovir treatment of tumor cells transduced with herpes simplex virus thymidine kinase

Wei

Chao²,

Shih

et al. 1999

Gene Ther

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Transduction of cancer cells with herpes simplex virus thy-HSVtk-transduced tumor cells after the cell cycle arrest midine kinase gene (HSVtk) followed by prodrug gancicloand before apoptosis. Increased expression of FasL could vir (GCV) treatment has been shown to induce apoptosis. also be observed in vivo in HSVtk-transduced tumors In this study, four murine tumors including B16F10 melainduced to regress by GCV treatment. Enzyme measurenoma, NG4TL4 sarcoma, H6 hepatoma and 1MEA 7R.1 ments using specific substrate showed that the caspase-3 hepatoma were found to vary in sensitivity to this gene activation followed kinetically the FasL expression. More therapy strategy in vitro but, at effective doses of GCV, the than half of the HSVtk/GCV-induced cell death could be HSVtk-transduced cells of all four tumors showed similar abrogated by addition to the cell culture medium of a spekinetics of early rise in p53 protein levels, then cell cycle cific antisense oligonucleotide to block FasL synthesis, a S-/G2-phase arrest and finally signs of apoptosis. Immunorecombinant Fas/Fc chimeric protein to compete with Fas blot analyses revealed that Fas (CD95/APO-1), Fas ligand receptor for FasL binding, or cell-permeable specific tetra-(FasL) and two downstream mediators, RIP and caspase-3 peptide inhibitors of caspase-3 or caspase-8. (CPP32, YAMA, Apopain) were increased in GCV-treated

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Fas-induced Activation of the Cell Death-related Protease CPP32 Is Inhibited by Bcl-2 and by ICE Family Protease Inhibitors

Cited by 293 publications

References 46 publications

Retinoid-related molecules require caspase 9 for the effective release of Smac and the rapid induction of apoptosis

Retinoid-related molecules require caspase 9 for the effective release of Smac and the rapid induction of apoptosis

Differential Effects of Bcl-2 on Cell Death Triggered under ATP-Depleting Conditions

Involvement of Fas (CD95/APO-1) and Fas ligand in apoptosis induced by ganciclovir treatment of tumor cells transduced with herpes simplex virus thymidine kinase

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