| TRAIL-induced apoptosis of human melanoma cells involves activation of caspase-4. | |
| | |
MedLine Citation:
|
PMID: 20514521 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Although it is conventionally regarded as an inflammatory caspase, recent studies have shown that caspase-4 plays a role in induction of apoptosis by endoplasmic reticulum (ER) stress. We report here that activation of caspase-4 is also involved in induction of apoptosis by TNF-related apoptosis-inducing ligand (TRAIL) in human melanoma cells. Treatment with TRAIL resulted in activation of caspase-4. This appeared to be mediated by caspase-3, in that caspase-4 was activated later than caspase-8, -9, and -3, and that inhibition of caspase-3 blocked TRAIL-induced caspase-4 activation. Notably, TRAIL triggered ER stress in melanoma cells as shown by up-regulation of the GRP78 protein and the spliced form of XBP-1 mRNA. This seemed to be necessary for activation of caspase-4, as activation of caspase-3 by agents that did not trigger ER stress did not cause activation of caspase-4. Importantly, inhibition of caspase-4 also partially blocked caspase-3 activation, suggesting that activation of caspase-4 may be positive feed-back mechanism to further enhance caspase-3 activation. Collectively, these results show that activation of caspase-4 contributes to TRAIL-induced apoptosis and is associated with induction of ER stress by TRAIL in melanoma cells, and may have important implications for improving therapeutic efficacies of TRAIL in melanoma. |
| | |
Authors:
|
Zhi Gang Mao; Chen Chen Jiang; Fan Yang; Rick F Thorne; Peter Hersey; Xu Dong Zhang |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Apoptosis : an international journal on programmed cell death Volume: 15 ISSN: 1573-675X ISO Abbreviation: Apoptosis Publication Date: 2010 Oct |
Date Detail:
|
Created Date: 2010-10-01 Completed Date: 2010-12-30 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9712129 Medline TA: Apoptosis Country: United States |
Other Details:
|
Languages: eng Pagination: 1211-22 Citation Subset: IM |
Affiliation:
|
Immunology and Oncology Unit, Newcastle Misericordiae Hospital, Room 443, David Maddison Clinical Sciences Building, Cnr. King and Watt Streets, Newcastle, NSW, 2300, Australia. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Apoptosis* Blotting, Western Caspase 3 / metabolism Caspases, Initiator / antagonists & inhibitors, metabolism* Cell Line, Tumor DNA-Binding Proteins / genetics, metabolism Endoplasmic Reticulum / metabolism Enzyme Activation Gene Expression Heat-Shock Proteins / genetics, metabolism Humans Melanoma / metabolism*, pathology* Mice RNA Splicing RNA, Small Interfering Rabbits Recombinant Proteins Stress, Physiological TNF-Related Apoptosis-Inducing Ligand / metabolism*, pharmacology Transcription Factors / genetics, metabolism Up-Regulation |
| Chemical | |
Reg. No./Substance:
|
0/DNA-Binding Proteins; 0/Heat-Shock Proteins; 0/RNA, Small Interfering; 0/Recombinant Proteins; 0/TNF-Related Apoptosis-Inducing Ligand; 0/TNFSF10 protein, human; 0/Transcription Factors; 0/molecular chaperone GRP78; 0/regulatory factor X transcription factors; EC 3.4.22.-/CASP4 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases, Initiator |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: CBCL behavior problems of post-institutionalized international adoptees.
Next Document: Predicting survival and morbidity-free survival to very old age.