In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine protease containing two FADD-like domains.

Fernandes-Alnemri, Teresa; Armstrong, Robert C.; Krebs, Joseph F.; Srinivasula, Srinivasa M.; Wang, Limin; Bullrich, Florencia; Fritz, Lawrence C.; Trapani, Joseph A.; Tomaselli, Kevin J.; Litwack, Gerald; Alnemri, Emad S.

doi:10.1073/pnas.93.15.7464

Cited by 699 publications

(540 citation statements)

References 30 publications

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“…Interestingly, the labeled caspases showed di erent sensitivities to the inhibitor (F20&F174F224F254F19; S20&S174S224S19). This is consistent with previous studies showing signi®cant di erences in Ki values for DEVD-CHO among caspases (Fernandes-Alnemri et al, 1995b. Then, the e ects of DEVD-CHO on the labeling of recombinant caspases were examined for comparison.…”

Section: Stepwise Activation Of Caspases In Apoptotic Jurkat Cells Resupporting

confidence: 89%

“…It remained to be clari®ed whether caspase(s) exist that have a nities too low to be labeled by YV(bio)KDaomk. The protease activity cleaving DEVD-MCA, ā uorogenic substrate for caspases (Boldin et al, 1996;Duan et al, 1996b;Fernandes-Alnemri et al, 1996;Henkart, 1996), began to rise at 30 min of Fasstimulation, coincident with the appearance of F17.5, and at 30 min of staurosporine-treatment, synchronous with the appearance of S22 and S20 (Figure 4). Therefore, it was likely that the a nity-labeling method resolved the active caspases responsible for the cleavage of DEVD-MCA.…”

Section: Stepwise Activation Of Caspases In Apoptotic Jurkat Cells Rementioning

confidence: 99%

“…The cascade hypothesis is mainly based on demonstrations that recombinant caspases-1, 3, 4, 6/a, and 10 can process precursor(s) of other caspase(s) (Faucheu et al, 1995;Fernandes-Alnemri et al, 1995bLiu et al, 1996;Srinivasula et al, 1996). However, most of those data were derived from in vitro experiments using recombinant proteins expressed in bacteria, or from analysis of cells in which caspases were overexpressed.…”

Section: Introductionmentioning

confidence: 99%

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Affinity labeling displays the stepwise activation of ICE-related proteases by Fas, staurosporine, and CrmA-sensitive caspase-8

et al. 1997

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The activation of multiple interleukin-1b converting enzyme-related proteases (caspases) in apoptotic mammalian cells raises questions as to whether the multiple active caspases have distinct roles in apoptotic execution as well as how these proteases are organized in apoptotic signaling pathways. Here we used an a nity-labeling agent, YV(bio)KD-aomk, to investigate the caspases activated during apoptotic cell death. YV(bio)KD-aomk identi®ed six distinct polypeptides corresponding to active caspases in Fas-stimulated Jurkat T cells. On staurosporine treatment, four polypeptides were detected. Competition experiments showed that the labeled caspases have distinct substrate preferences. Stepwise appearance of the labeled caspases in each cell death event was consistent with the view that the activated caspases are organized into protease cascades. Moreover, we found that stepwise activation of caspases similar to that induced by Fas ligation is triggered by exposing non-apoptotic Jurkat cell extracts to caspase-8 (MACH/FLICE/Mch5). Conversely, CrmA protein, a viral suppressor of Fas-induced apoptosis, inhibited the protease activity of caspase-8. Overall, these ®ndings provide evidence that caspase-8, a CrmA-sensitive protease, is responsible for initiating the stepwise activation of multiple caspases in Fas-stimulated cells.

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Section: Stepwise Activation Of Caspases In Apoptotic Jurkat Cells Resupporting

confidence: 89%

Section: Stepwise Activation Of Caspases In Apoptotic Jurkat Cells Rementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Affinity labeling displays the stepwise activation of ICE-related proteases by Fas, staurosporine, and CrmA-sensitive caspase-8

et al. 1997

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“…[18][19][20] This provokes the self proteolysis and activation of the initiator caspase, which then directly cleaves and activates effector caspases. [21][22][23] The Bcl-2 family member Bid is cleaved by caspase 8 and targeted to the mitochondria, where it induces cytochrome c release and unleashes the intrinsic apoptotic machinery, providing a direct link between both apoptotic pathways. 24,25 In addition, caspase 8 can be activated independently of death receptor-mediated signals by certain anticancer drugs.…”

Section: Introductionmentioning

confidence: 99%

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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“…These cysteine-related proteases, named caspases, are synthesized as inactive proenzymes which are activated following cleavage at speci®c aspartate cleavage sites (Alnemri, 1997). Some caspases may activate other members of the family and ®nal activation may also result from autoprocessing as reported for caspase-3 (Fernandes- Alnemri et al, 1996;Martin et al, 1996). The importance of caspases has been demonstrated in di erent systems.…”

Section: Introductionmentioning

confidence: 99%

Role of caspases and possible involvement of retinoblastoma protein during TGFβ-mediated apoptosis of human B lymphocytes

et al. 1999

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In this study, we investigated the involvement of caspases in TGFb-induced apoptosis in human B cells. Our results show that TGFb-mediated nuclear fragmentation, observed in the Epstein ± Barr virus-negative Burkitt's Lymphoma cell line BL41, was abolished in the presence of the tripeptide caspase inhibitor ZVAD-fmk or the speci®c caspase-3 inhibitor DEVD-fmk. Other apoptotic manifestations such as cell shrinkage, surface phosphatidylserine expression and chromatin condensation were strongly inhibited by ZVAD-fmk but only partially by DEVD-fmk. This suggests that other caspases in addition to caspase-3 control these apoptotis-associated features. Speci®c activation of caspase-3 during TGFbinduced apoptosis was demonstrated by the DEVD-fmksensitive expression of the active p17 subunit of caspase-3 and by in vivo cleavage of PARP. In addition, TGFb treatment of BL41 promoted the expression of both dephosphorylated and truncated forms of the retinoblastoma protein. Inhibition of caspase-3 activity abolished both nuclear fragmentation and expression of the truncated retinoblastoma protein, without modifying the G1 cell cycle arrest induced by TGFb. Our data thus demonstrate that TGFb-induced apoptosis of lymphoma B lymphocytes is dependent on caspase activation and involves caspase-dependent cleavage of the retinoblastoma protein.

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In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine protease containing two FADD-like domains.

Cited by 699 publications

References 30 publications

Affinity labeling displays the stepwise activation of ICE-related proteases by Fas, staurosporine, and CrmA-sensitive caspase-8

Affinity labeling displays the stepwise activation of ICE-related proteases by Fas, staurosporine, and CrmA-sensitive caspase-8

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

Role of caspases and possible involvement of retinoblastoma protein during TGFβ-mediated apoptosis of human B lymphocytes

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