Proteases, proteasomes and apoptosis: breaking Ub is hard to do

Taylor, Rebecca C.; Adrain, Colin; Martin, Séamus J.

doi:10.1038/sj.cdd.4401703

Cited by 12 publications

(10 citation statements)

References 33 publications

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“…Evidence suggests that proteasome inhibitors prevent apoptosis in various settings (4,20,25,46,47,50), while other data indicate that proteasome inhibitors, either alone or in combination with death-inducing stimuli, cause apoptosis (1,22,42,50). Specifically, proteasome inhibitors are effective in killing cancer cells while sparing normal cells (1,47,50). Our results demonstrate that in renal cells proteasome inhibitors protect antiapoptotic proteins from proteasome-mediated degradation, which leads to cell survival.…”

Section: Discussionmentioning

confidence: 57%

“…The proteasome system is known to control levels of the Bcl-2 family of proteins (6,16,36,50), so part of this protective mechanism in LLC-PK 1 cells might be mediated by Mcl-1 accumulation due to proteasome inhibition. Evidence suggests that proteasome inhibitors prevent apoptosis in various settings (4,20,25,46,47,50), while other data indicate that proteasome inhibitors, either alone or in combination with death-inducing stimuli, cause apoptosis (1,22,42,50). Specifically, proteasome inhibitors are effective in killing cancer cells while sparing normal cells (1,47,50).…”

Section: Discussionmentioning

confidence: 99%

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Mcl-1 is downregulated in cisplatin-induced apoptosis, and proteasome inhibitors restore Mcl-1 and promote survival in renal tubular epithelial cells

Yang¹,

Kaushal²,

Shah³

et al. 2007

American Journal of Physiology-Renal Physiology

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Mcl-1 is an antiapoptotic member of the Bcl-2 family that plays an important role in cell survival. We demonstrate that proteasome-dependent regulation of Mcl-1 plays a critical role in renal tubular epithelial cell injury from cisplatin. Protein levels of Mcl-1 rapidly declined in a time-dependent manner following cisplatin treatment of LLC-PK(1) cells. However, mRNA levels of Mcl-1 were not altered following cisplatin treatment. Expression of other antiapoptotic members of the Bcl-2 family such as Bcl-2 and BclxL was not affected by cisplatin treatment. Cisplatin-induced loss of Mcl-1 occurs at the same time as the mitochondrial release of cytochrome c, activation of caspase-3, and initiation of apoptosis. Treatment of cells with cycloheximide, a protein synthesis inhibitor, revealed rapid turnover of Mcl-1. In addition, treatment with cycloheximide in the presence or absence of cisplatin demonstrated that cisplatin-induced loss of Mcl-1 results from posttranslational degradation rather than transcriptional inhibition. Overexpression of Mcl-1 protected cells from cisplatin-induced caspase-3 activation and apoptosis. Preincubating cells with the proteasome inhibitor MG-132 or lactacystin not only restored cisplatin-induced loss of Mcl-1 but also resulted in an accumulation of Mcl-1 that exceeded basal levels; however, Bcl-2 and BclxL levels did not change in response to MG-132 or lactacystin. The proteasome inhibitors effectively blocked cisplatin-induced mitochondrial release of cytochrome c, caspase-3 activation, and apoptosis. These studies suggest that proteasome regulation of Mcl-1 is crucial in the cisplatin-induced apoptosis via the mitochondrial apoptotic pathway and that Mcl-1 is an important therapeutic target in cisplatin injury to renal tubular epithelial cells.

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Mcl-1 is downregulated in cisplatin-induced apoptosis, and proteasome inhibitors restore Mcl-1 and promote survival in renal tubular epithelial cells

Yang¹,

Kaushal²,

Shah³

et al. 2007

American Journal of Physiology-Renal Physiology

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show abstract

“…From previous reports, several pro-apoptotic factors and signaling pathways have been shown to be involved in ER stress-induced cell death, including calpain, Cysteine aspartyl protease (caspase-4) (human), caspase-12 (murine), CHOP/GADD153, TRAF2, ASK-1, JNK, and pro-apoptotic Bcl-2 family members, among others. [7][8][9][10] In many instances, caspases have been implicated in this cell death pathway, on the grounds that broadspectrum caspase inhibitors block cell death. In some cases, however, cell death is not fully blocked by caspase inhibitors, suggesting that caspase-independent mechanisms may contribute to the execution of ER stress-induced cell death.…”

mentioning

confidence: 99%

Endoplasmic reticulum stress-induced cell death mediated by the proteasome

et al. 2007

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“…8 This is highlighted by several manuscripts in this issue. [9][10][11][12][13] However, the most striking example of the involvement of the UPS in apoptosis is provided by the fact that some apoptosisrelated proteins contain domains with E3-like activity owing to a unique C-terminal RING domain, as elegantly described by Vaux, and Silke 9 and in the Swiss-German humour of Pascal Meier. 10 These are the inhibitor of apoptosis (IAP) family of proteins, including XIAP, c-IAP-1 and c-IAP-2.…”

mentioning

confidence: 99%

Discovery of the ubiquitin proteasome system and its involvement in apoptosis

Melino¹

2005

Cell Death Differ

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Proteases, proteasomes and apoptosis: breaking Ub is hard to do

Cited by 12 publications

References 33 publications

Mcl-1 is downregulated in cisplatin-induced apoptosis, and proteasome inhibitors restore Mcl-1 and promote survival in renal tubular epithelial cells

Mcl-1 is downregulated in cisplatin-induced apoptosis, and proteasome inhibitors restore Mcl-1 and promote survival in renal tubular epithelial cells

Endoplasmic reticulum stress-induced cell death mediated by the proteasome

Discovery of the ubiquitin proteasome system and its involvement in apoptosis

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