Enhancement of CPP32-like Activity in the TNF-Treated U937 Cells by the Proteasome Inhibitors

Fujita, Eriko; Mukasa, Takeshi; Tsukahara, Toshibumi; Arahata, Kiichi; Ōmura, Satoshi; Momoi, Takashi

doi:10.1006/bbrc.1996.0986

Cited by 56 publications

(45 citation statements)

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“…Whereas the function of caspases is well defined, the exact role of the ubiquitin-proteasome system in apoptosis is far from being elucidated. Several studies showed that the inhibition of the proteasome blocked apoptosis in various settings (18,20,46), whereas others demonstrated efficient induction of apoptosis when cells were treated with PIs either alone or in combination with various death-inducing stimuli (8,11,19,30,60). As the antiapoptotic activities of PIs were described for resting thymocytes and differentiated neuronal cells and the proapoptotic effects were described for various tumor cell lines, it was postulated that the requirement of proteasomal activity for the progression or inhibition of apoptosis critically depends on the proliferative status of the cells (9,41).…”

Section: Discussionmentioning

confidence: 99%

“…Promising results were obtained from studies showing that the cytotoxic potential of TRAIL was synergistically enhanced by a combined treatment with chemotherapeutics (16) or radiation (36). Also, the simultaneous treatment with proteasomal inhibitors (PIs), such as bortezomib (PS-341), lactacystin, or MG-132, yielded encouraging results, as all of these compounds synergistically accelerated and enhanced TRAIL-or TNF-induced apoptosis in a variety of tumor cells (11,19,30,60). In view of this success, the proteasome inhibitor bortezomib has recently entered clinical practice as a treatment for multiple myeloma and is also undergoing clinical trials for other types of cancer (45,58).…”

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confidence: 99%

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The Proteasome Is Required for Rapid Initiation of Death Receptor-Induced Apoptosis

Sohn

Totzke

Eßmann

et al. 2006

Molecular and Cellular Biology

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show that once these proteins were eliminated, either by long-term treatment with death receptor ligands or by siRNA-mediated suppression, active caspases accumulated to an even larger extent in the presence of PIs. Together, our data support a biphasic role for the proteasome in apoptosis, as they show that its constitutive activity is crucial for the rapid initiation of the death program by eliminating antiapoptotic proteins, whereas at later stages, the proteasome acts in an antiapoptotic manner due to the proteolysis of caspases. Thus, for a successful PI-based tumor therapy, it is crucial to carefully evaluate basal proteasomal activity and the status of antiapoptotic proteins, as their PI-mediated prolonged stability might even cause adverse effects, leading to the survival of a tumor.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The Proteasome Is Required for Rapid Initiation of Death Receptor-Induced Apoptosis

Sohn

Totzke

Eßmann

et al. 2006

Molecular and Cellular Biology

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“…ICElike activity was not stimulated, but a peptide inhibitor of CPP32-like activity both inhibited the generation of CPP32-like activity, and the decreased cell viability induced by combinations of TNF and a proteasome inhibitor. 78 Subsequent investigations confirmed PARP cleavage in U937 cells after proteasomal inhibition. 53 In mouse lymphoma RVC cells, however, while an inhibitor of CPP32-like activity did decrease DNA fragmentation induced by proteasome inhibition, ICE inhibitors did not impact on this process.…”

Section: The Proteasome and The Apoptotic Cascadementioning

confidence: 91%

The role of the ubiquitin-proteasome pathway in apoptosis

1999

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Coordinated intracellular protein degradation mediated by the ubiquitin-proteasome pathway is crucial to a vast array of cellular processes including orderly progression through the mitotic cycle. Similarly important to both the fates of individual cells, as well as to the normal function of multicellular organisms, is the process of apoptosis, or programmed cell death. Execution of this latter process has been known for some time to be intimately associated with the activity of caspases, a family of proteases related to interleukin-1-b-converting enzyme. Evidence is now accumulating, however, that the ubiquitin-proteasome system itself plays an important role in apoptosis, and some of the cellular pathways that are impacted upon by the proteasome, and may lead to apoptosis, are beginning to be dissected. This review provides a summary of the experimental basis by which components of the ubiquitinproteasome pathway have been linked to apoptosis, and attempts are made to formulate a hypothesis about its role in this process.

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“…91 The role of the proteasome in maintaining cell viability is likely heavily dependent upon its ability to degrade proapoptotic as well as antiapoptotic proteins, 92-94 a process which is dictated by currently ill-defined factors which dictate substrate specificity. In neuronal cells, proteasome inhibitors can, in some instances, protect against apoptosis by degrading caspases themselves, 95 by acting upstream of caspase activation, 96 by enhancing the degradation of such targets as BH-3 proapoptotic proteins 94 and cytotoxic kinases, 97 as well as by inducing the expression of molecular chaperones and enhancing MAPK phosphorylation. 94,98,99 A fine balance must therefore exist to regulate cell fate decisions in response to alterations in proteasomal function and presentation of substrates.…”

Section: Proteasomal Regulation Of Activated Caspases Is Likely Critimentioning

confidence: 99%

The kinder side of killer proteases: Caspase activation contributes to neuroprotection and CNS remodeling

McLaughlin

2004

Apoptosis

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Caspases are a family of cysteine proteases that are expressed as inactive zymogens and undergo proteolytic maturation in a sequential manner in which initiator caspases cleave and activate the effector caspases 3, 6 and 7. Effector caspases cleave structural proteins, signaling molecules, DNA repair enzymes and proteins which inhibit apoptosis. Activation of effector, or executioner, caspases has historically been viewed as a terminal event in the process of programmed cell death. Emerging evidence now suggests a broader role for activated caspases in cellular maturation, differentiation and other non-lethal events. The importance of activated caspases in normal cell development and signaling has recently been extended to the CNS where these proteases have been shown to contribute to axon guidance, synaptic plasticity and neuroprotection. This review will focus on the adaptive roles activated caspases in maintaining viability, the mechanisms by which caspases are held in check so as not produce apoptotic cell death and the ramifications of these observations in the treatment of neurological disorders.

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Enhancement of CPP32-like Activity in the TNF-Treated U937 Cells by the Proteasome Inhibitors

Cited by 56 publications

References 0 publications

The Proteasome Is Required for Rapid Initiation of Death Receptor-Induced Apoptosis

The Proteasome Is Required for Rapid Initiation of Death Receptor-Induced Apoptosis

The role of the ubiquitin-proteasome pathway in apoptosis

The kinder side of killer proteases: Caspase activation contributes to neuroprotection and CNS remodeling

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