An interleukin‐1β‐converting enzyme‐like protease is a common mediator of apoptosis in thymocytes

Fearnhead, Howard O.; Dinsdale, David; Cohen, Gerald M.

doi:10.1016/0014-5793(95)01228-7

Cited by 101 publications

(76 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The point of convergence of these pathways at the level of eIF4G is most likely the activation of one or more`executioner' caspases (Longthorne and Williams, 1997; Kamada et al, 1997;Cohen, 1997). This is consistent with the ability of the caspase inhibitors (Z-VAD.FMK and Z-DEVD.FMK; Dolle et al, 1994;Fearnhead et al, 1995;Perry et al, 1997;Juo et al, 1997), but not calpain or proteosome inhibitors (data not shown), to block the disappearance of eIF4G regardless of the apoptosis-inducing stimulus.…”

Section: Discussionsupporting

confidence: 57%

“…Apoptosis is characterized by a series of cellular changes that lead ultimately to cell death (Hale et al, 1996;Rowan and Fisher, 1997;Nagata, 1997;Salvesen and Dixit, 1997). An essential aspect of these events is the sequential activation of a number of proteases with limited substrate speci®cities, the caspases (Fearnhead et al, 1995;Tewari et al, 1995;Enari et al, 1996;Salvesen and Dixit, 1997;Cohen, 1997;Longthorne and Williams, 1997;Ohta et al, 1997). Intensive research in recent years has investigated the properties of these enzymes, the nature of some of their substrates, and their relative relationships in the protease cascades required for execution of the apoptotic programme.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Degradation of eukaryotic polypeptide chain initiation factor (eIF) 4G in response to induction of apoptosis in human lymphoma cell lines

1998

View full text Add to dashboard Cite

We have investigated the e ect of inducing apoptosis in BJAB and Jurkat cells on the cellular content of several polypeptide chain initiation factors. Serum deprivation results in inhibition of protein synthesis and induction of apoptosis in BJAB cells; at early times, there is selective degradation of polypeptide initiation factor eIF4G but no major losses of other key initiation factors. The disappearance of full length eIF4G is accompanied by the appearance of smaller forms of the protein, including a major product of approximately 76 kDa. Apoptosis induced by cycloheximide results in similar e ects. Both total cytoplasmic eIF4G and eIF4G associated with eIF4E are degraded with a half-life of 2 ± 4 h under these conditions. Treatment of serum-starved or cycloheximide-treated cells with Z-VAD.FMK or Z-DEVD.FMK, which inhibit caspases required for apoptosis, protects eIF4G from degradation and blocks the appearance of the ca. 76 kDa product. Exposure of BJAB cells to rapamycin rapidly inhibits protein synthesis but does not lead to acute degradation of eIF4G. In both BJAB and Jurkat cells induction of apoptosis with anti-Fas antibody or etoposide also results in the selective loss of eIF4G, which is inhibitable by Z-VAD.FMK. These data suggest that eIF4G is selectively targeted for cleavage as cells undergo apoptosis and is a substrate for proteases activated during this process.

show abstract

Section: Discussionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Degradation of eukaryotic polypeptide chain initiation factor (eIF) 4G in response to induction of apoptosis in human lymphoma cell lines

1998

View full text Add to dashboard Cite

show abstract

“…In order to assess the role of caspases in the execution phase of apoptosis in B-CLL cells, we used Z-VAD.fmk, a cell permeable caspase inhibitor, which inhibits apoptosis in many different model systems. 21,26,27 Z-VAD.fmk (100 m) inhibited spontaneous apoptosis in all but one of the patient samples examined (Table 1) supporting the involvement of caspases in the spontaneous apoptosis of CLL cells. In order to obtain more definitive evidence for the involvement of caspases, we examined the processing/activation of the effector caspases as well as the proteolysis of PARP, which has been used as a marker of apoptosis.…”

Section: Inhibition Of Spontaneous Apoptosis In Cll Cells By Z-vadfmkmentioning

confidence: 62%

Processing/activation of caspases, -3 and -7 and -8 but not caspase-2, in the induction of apoptosis in B-chronic lymphocytic leukemia cells

et al. 1998

View full text Add to dashboard Cite

Chlorambucil and prednisolone, two commonly used drugs in the treatment of chronic lymphocytic leukemia (CLL), induce apoptosis in CLL cells. We have investigated the involvement in this apoptotic cell death of caspases, which cleave critical cellular substrates thereby acting as the executioners of the apoptotic process. Induction of spontaneous or chlorambucil/ prednisolone-induced apoptosis of freshly isolated B-CLL cells in culture resulted in the activation of the 'effector' caspases, -3 and -7, but generally not of caspase-2. Activation of caspases-3 and -7 was accompanied by the proteolysis of the DNA repair enzyme, poly (ADP-ribose) polymerase. Induction of apoptosis was also accompanied by the processing of caspase-8, the extent of which varied between patients. Induction of apoptosis and processing of all the caspases was inhibited by the cell permeable caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethyl ketone (Z-VAD.fmk). Our results demonstrate a key role for the activation and processing of caspases in the execution phase of apoptosis in CLL cells. Apoptosis of CLL cells resulted in the selective activation of some but not all caspases. Our results suggest that the dysregulation of apoptosis observed in CLL may be due to the signalling leading to the activation of caspases rather than a deletion of pro-caspases. High levels of caspase-8 in CLL cells in conjunction with low levels of CD95 receptor may offer new therapeutic opportunities for the treatment of CLL.

show abstract

“…Among the numerous ICE-like protease inhibitors, Z.VAD is a broad-spectrum antagonist of numerous proteases that inhibits apoptosis in mammalian and insects cells [46,47]. These data suggest that the ICE pro-r Mitochondrial PT…”

Section: Proteases As Mediators Of Apoptosismentioning

confidence: 94%

Mitochondria and programmed cell death: back to the future

Petit¹,

Susin²,

Zamzami³

et al. 1996

FEBS Letters

477

250

View full text Add to dashboard Cite

tbstract Programmed cell death, or apoptosis, has in the past few years undoubtedly become one of the most intensively investigated biological processes. However, fundamental queslions concerning the molecular and biochemical mechanisms remain to be elucidated. The central question concerns the biochemical steps shared by the numerous death induction pathways elicited by different stimuli. Heterogeneous death signals precede a common effector phase during which cells pass a threshold of'no return' and are engaged in a degradation phase where they acquire the typical onset of late apoptosis. Alterations in mitochondrial permeability transition linked to membrane potential disruption precede nuclear and plasma membrane changes. In vitro induction of permeability transition in isolated mitochondria provokes the release of a protein factor capable of inducing nuclear chromatin condensation and fragmentation. Yhis permeability transition is regulated by multiple endogenous effectors, including members of the bcl-2 gene family. Inhibition of these effects prevents apoptosis.

show abstract

An interleukin‐1β‐converting enzyme‐like protease is a common mediator of apoptosis in thymocytes

Cited by 101 publications

References 38 publications

Degradation of eukaryotic polypeptide chain initiation factor (eIF) 4G in response to induction of apoptosis in human lymphoma cell lines

Degradation of eukaryotic polypeptide chain initiation factor (eIF) 4G in response to induction of apoptosis in human lymphoma cell lines

Processing/activation of caspases, -3 and -7 and -8 but not caspase-2, in the induction of apoptosis in B-chronic lymphocytic leukemia cells

Mitochondria and programmed cell death: back to the future

Contact Info

Product

Resources

About