Caspase-8 Activation and Bid Cleavage Contribute to MCF7 Cellular Execution in a Caspase-3-dependent Manner during Staurosporine-mediated Apoptosis

Tang, Damu; Lahti, Jill M.; Kidd, Vincent J.

doi:10.1074/jbc.275.13.9303

Cited by 233 publications

(170 citation statements)

References 27 publications

(20 reference statements)

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“…This suggests that Bid can be cleaved also by caspases other than caspase-8. Indeed, our data in caspase-3-transfected MCF7 cells as well as meanwhile published reports (Slee et al, 2000;Tang et al, 2000) suggest that Bid is not only cleaved by caspase-8 but also by caspase-3. Since the caspase-8-independent activation of Bid occurs downstream of the mitochondrial cytochrome c release, it might initiate an ampli®cation loop that enhances the relocalization of cytochrome c by anticancer drugs.…”

Section: Discussionsupporting

confidence: 86%

Caspase-8/FLICE functions as an executioner caspase in anticancer drug-induced apoptosis

et al. 2000

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Caspase-8 plays an essential role in apoptosis triggered by death receptors. Through the cleavage of Bid, a proapoptotic Bcl-2 member, it further activates the mitochondrial cytochrome c/Apaf-1 pathway. Because caspase-8 can be processed also by anticancer drugs independently of death receptors, we investigated its exact role and order in the caspase cascade. We show that in Jurkat cells either de®cient for caspase-8 or overexpressing its inhibitor c-FLIP apoptosis mediated by CD95, but not by anticancer drugs was inhibited. In the absence of active caspase-8, anticancer drugs still induced the processing of caspase-9, -3 and Bid, indicating that Bid cleavage does not require caspase-8. Overexpression of Bcl-x L prevented the processing of caspase-8 as well as caspase-9, -6 and Bid in response to drugs, but was less e ective in CD95-induced apoptosis. Similar responses were observed by overexpression of a dominant-negative caspase-9 mutant. To further determine the order of caspase-8 activation, we employed MCF7 cells lacking caspase-3. In contrast to caspase-9 that was cleaved in these cells, anticancer drugs induced caspase-8 activation only in caspase-3 transfected MCF7 cells. Thus, our data indicate that, unlike its proximal role in receptor signaling, in the mitochondrial pathway caspase-8 rather functions as an amplifying executioner caspase.

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Section: Discussionsupporting

confidence: 86%

Caspase-8/FLICE functions as an executioner caspase in anticancer drug-induced apoptosis

et al. 2000

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“…Cross-talk between these pathways is the result of the cleavage of the pro-apoptotic BCL-2 family member Bid. Cleaved and activated caspase-8 cannot only serve to activate caspase 3, which is the executioner caspase, but also cleave full-length Bid into a truncated version (tBid) [57]. tBid then interacts with pro-apoptotic Bax, to stimulate apoptotic signaling from the mitochondria [58].…”

Section: Pro-apoptotic Signaling Cross-talkmentioning

confidence: 99%

Death receptor-associated pro-apoptotic signaling in aged skeletal muscle

2006

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Tumor necrosis factor-alpha (TNF-α) is elevated in the serum as a result of aging and it promotes pro-apoptotic signaling upon binding to the type I TNF receptor. It is not known if activation of this apoptotic pathway contributes to the well-documented age-associated decline in muscle mass (i.e. sarcopenia). We tested the hypothesis that skeletal muscles from aged rodents would exhibit elevations in markers involved in the extrinsic apoptotic pathway when compared to muscles from young adult rodents, thereby contributing to an increased incidence of nuclear apoptosis in these muscles. The plantaris (fast) and soleus (slow) muscles were studied in young adult (5-7 mo, n = 8) and aged (33 mo, n = 8) Fischer 344 × Brown Norway rats. Muscles from aged rats were significantly smaller while exhibiting a greater incidence of apoptosis. Furthermore, muscles from aged rats had higher type I TNF receptor and Fas associated death domain protein (FADD) mRNA, protein contents for FADD, BCL-2 Interacting Domain (Bid), FLICE-inhibitory protein (FLIP), and enzymatic activities of caspase-8 and caspase-3 than muscles from young adult rats. Significant correlations were observed in the plantaris muscle between caspase activity and muscle weight and the apoptotic index, while similar relationships were not found in the soleus. These data demonstrate that pro-apoptotic signaling downstream of the TNF receptor is active in aged muscles. Furthermore, our data extend the previous demonstration that type II fibers are preferentially affected by aging and support the hypothesis that type II fiber containing skeletal muscles may be more susceptible to muscle mass loses via the extrinsic apoptotic pathway.

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“…In InB-SR expressing cells, processing to active caspase-3 (p17) is also promoted in comparison to the Ad.LacZ-transduced control cells. Furthermore, processing of procaspase-8 was slightly enhanced in InB-SR and shRNA.XIAP expressing cells, which is most likely the result of enhanced activation of caspase-3 because procaspase-8 is a substrate for active caspase-3 (70)(71)(72). The immunoblot data could be confirmed by a caspase-3 activity assay showing a significant increase in caspase-3 activity after TRAIL treatment in cells treated with Ad.shRNA.XIAP compared with cells transduced with the control vector Ad.shRNA.EGFP (Fig.…”

Section: Down-regulation Of Xiap Protein Levels By Rna Interference Imentioning

confidence: 99%

Constitutively Activated Nuclear Factor-κB, but not Induced NF-κB, Leads to TRAIL Resistance by Up-Regulation of X-Linked Inhibitor of Apoptosis Protein in Human Cancer Cells

Braeuer

Büneker

Mohr

et al. 2006

Molecular Cancer Research

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The tumor necrosis factor -related apoptosis-inducing ligand (TRAIL) is a potent inducer of apoptosis in most, but not all, cancer cells. The molecular factors regulating the sensitivity to TRAIL are still incompletely understood. The transcription factor nuclear factor-KB (NF-KB) has been implicated, but its exact role is controversial. We studied different cell lines displaying varying responses to TRAIL and found that TRAIL can activate NF-KB in all our cancer cell lines regardless of their TRAIL sensitivity. Inhibition of NF-KB via adenoviral expression of the IKB-A super-repressor only sensitized the TRAIL-resistant pancreatic cancer cell line Panc-1. Panc-1 cells harbor constitutively activated NF-KB, pointing to a possible role of preactivated NF-KB in protection from TRAIL. Furthermore, we could reduce X-linked inhibitor of apoptosis protein (XIAP) levels in Panc-1 cells by inhibition of constitutively activated NF-KB and sensitize Panc-1 cells to TRAIL by RNA interference against XIAP. These results implicate elevated XIAP levels caused by high basal NF-KB activity in TRAIL resistance and suggest that therapeutic strategies involving TRAIL can be abetted by inhibition of NF-KB and/or XIAP only in tumor cells with constitutively

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Caspase-8 Activation and Bid Cleavage Contribute to MCF7 Cellular Execution in a Caspase-3-dependent Manner during Staurosporine-mediated Apoptosis

Cited by 233 publications

References 27 publications

Caspase-8/FLICE functions as an executioner caspase in anticancer drug-induced apoptosis

Caspase-8/FLICE functions as an executioner caspase in anticancer drug-induced apoptosis

Death receptor-associated pro-apoptotic signaling in aged skeletal muscle

Constitutively Activated Nuclear Factor-κB, but not Induced NF-κB, Leads to TRAIL Resistance by Up-Regulation of X-Linked Inhibitor of Apoptosis Protein in Human Cancer Cells

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