Involvement of Cytoplasmic Serine Proteinase and CPP32 Subfamily in the Molecular Machinery of Caspase 3 Activation during Fas-Mediated Apoptosis

Suzuki, Atsushi; Iwasaki, Masaru; Wagai, Nobuhiko

doi:10.1006/excr.1997.3546

Cited by 29 publications

(39 citation statements)

References 26 publications

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“…Interestingly, p21 interacted with only procaspase 3, but not with activated caspase 3. During Fas-mediated apoptosis, the ®rst step of caspase 3 activation is the cleaving at p3 site (Suzuki et al, 1997b). So, p21 may bind to the p3 site of procaspase 3.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the procaspase 3/p21 complex formation is the ®rst resistance-machinery. If procaspase 3 is activated by the proteolysis by SP26 (Suzuki et al, 1997b), its activation can be suppressed by the binding of ILP to activated caspase 3. The activated caspase 3/ILP complex formation also lead to`cell survival'.…”

Section: Discussionmentioning

confidence: 99%

“…To examine a direct involvement of the CPP32 subfamily in Fas-mediated apoptosis, the e ect of a synthetic tetrapeptide inhibitor DEVD-CHO (Hasegawa et al, 1996;Suzuki et al, 1997b) on the activation of the CPP32 subfamily was investigated. When HepG2 cells showed Fas-mediated apoptosis upon stimulation by Fas Ab in the presence of actinomycin D, a drastic elevation of CPP32 subfamily activity ( Figure 2a) and the death prevention by DEVD-CHO (Figure 2b) were encountered.…”

Section: Cpp32 Subfamily During Fas-mediated Apoptosismentioning

confidence: 99%

“…Ten genes have been identi®ed as ICE/CED-3 homologue and these were recently termed the`caspase' family (Alnemri et al, 1996). Among caspases, an essential role of caspase 3 (CPP32/Yama/Apopain) in Fasmediated apoptosis has been reported (FernandesAlnemri et al, 1994;Hasegawa et al, 1996;Suzuki et al, 1997b). Caspase 3 exists in the cytoplasm of intact cells as a proenzyme form and is activated by proteolysis induced by the stimulation of Fas (Hasegawa et al, 1996;Suzuki et al, 1997b).…”

Section: Introductionmentioning

confidence: 99%

“…Among caspases, an essential role of caspase 3 (CPP32/Yama/Apopain) in Fasmediated apoptosis has been reported (FernandesAlnemri et al, 1994;Hasegawa et al, 1996;Suzuki et al, 1997b). Caspase 3 exists in the cytoplasm of intact cells as a proenzyme form and is activated by proteolysis induced by the stimulation of Fas (Hasegawa et al, 1996;Suzuki et al, 1997b). Caspase 3 is the essential factor in Fas-initiated death signaling, since it directly induces the activation of DNA fragmentation factor (DFF and Liu et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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Resistance to Fas-mediated apoptosis: activation of Caspase 3 is regulated by cell cycle regulator p21WAF1 and IAP gene family ILP

Suzuki¹,

Tsutomi²,

Akahane³

et al. 1998

Oncogene

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322

277

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The death receptor Fas transduces apoptotic death signaling mediated by caspases. In the present study, human hepatoma HepG2 cells showed the Fas-mediated apoptosis mediated by caspase, especially caspase 3, only in the presence of actinomycin D. Interestingly, cytosolic proteins extracted from intact HepG2 cells induced caspase 3 inactivation. Our results reveal that this inactivation was triggered by the direct inhibition of activated caspase 3 by IAP gene family ILP. In addition, a 53 kDa protein was co-immunoprecipitated with antihuman caspase 3 antibody from intact HepG2 cells. This protein was a complex-protein of procaspase 3 and the cell cycle regulator p21 WAF1 (p21). P21 bound to only procaspase 3, but not to activated caspase 3. We also demonstrate that p21 protein-loaded HepG2 cells resist to Fas-mediated apoptosis even in the presence of actinomycin D. Here we report that caspase 3 inactivation for the resistance to Fas-mediated apoptosis is induced by a procaspase 3/p21 complex formation and direct inhibition of activated caspase 3 by ILP.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Cpp32 Subfamily During Fas-mediated Apoptosismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Resistance to Fas-mediated apoptosis: activation of Caspase 3 is regulated by cell cycle regulator p21WAF1 and IAP gene family ILP

Suzuki¹,

Tsutomi²,

Akahane³

et al. 1998

Oncogene

Self Cite

322

277

View full text Add to dashboard Cite

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Chemotherapeutic Drug Activation of the AP24 Protease in Apoptosis: Requirement for Caspase 3-like-Proteases

Wright

Schellenberger²,

Wang³

et al. 1998

Biochemical and Biophysical Research Communications

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Two Types of Death of Poliovirus-Infected Cells: Caspase Involvement in the Apoptosis but Not Cytopathic Effect

et al. 1998

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The death of poliovirus-infected cells may occur in two forms: canonical cytopathic effect (CPE) (on productive infections) or apoptosis (when the viral reproduction is hindered by certain drugs or some other restrictive conditions). Morphological manifestations of the CPE and apoptosis, being distinct, share some traits (e.g., chromatin condensation and nuclear deformation). It was shown here that a permeable caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-(OMe) fluoromethyl ketone (zVAD.fmk), prevented the development of the poliovirus-induced apoptosis on abortive infection. The apoptotic pathway could be dissected by an inhibitor of chymotrypsin-like serine proteases, N-tosyl-l-phenylalanine chloromethyl ketone (TPCK), which prevented the cleavage of DNA to oligonucleosome-sized pieces and nuclear fragmentation but did not suppress cellular shrinkage, cytoplasmic blebbing, and partial chromatin condensation. These results demonstrate that caspase activation is involved in the execution phase of the viral apoptosis and suggest that a nuclear subset of the apoptotic program is under a separate control, involving a TPCK-sensitive event. Neither zVAD.fmk nor TPCK, at the concentrations affecting the apoptotic response, exerted appreciable influence on the virus growth or cellular pathological changes on productive infection, indicating that the pathways leading to the poliovirus-evoked CPE and apoptosis are different.

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Involvement of Cytoplasmic Serine Proteinase and CPP32 Subfamily in the Molecular Machinery of Caspase 3 Activation during Fas-Mediated Apoptosis

Cited by 29 publications

References 26 publications

Resistance to Fas-mediated apoptosis: activation of Caspase 3 is regulated by cell cycle regulator p21WAF1 and IAP gene family ILP

Resistance to Fas-mediated apoptosis: activation of Caspase 3 is regulated by cell cycle regulator p21WAF1 and IAP gene family ILP

Chemotherapeutic Drug Activation of the AP24 Protease in Apoptosis: Requirement for Caspase 3-like-Proteases

Two Types of Death of Poliovirus-Infected Cells: Caspase Involvement in the Apoptosis but Not Cytopathic Effect

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