ArticleOncogene2011
Caspase-3 cleaves XIAP in a positive feedback loop to sensitize melanoma cells to TRAIL-induced apoptosis.
Article in Oncogene, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 80 citations in OpenAlex.
- Truncated LKB1 nonenzymatically enhances Fas-induced apoptosis by acting as a surrogate of Smac.Cell death discovery · 2025Article
- Pharmacological targeting of caspase-8/c-FLIPCommunications biology · 2025Article
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- XIAP promotes melanoma growth by inducing tumour neutrophil infiltration.EMBO reports · 2022Article
- Cell-to-cell variability in inducible Caspase9-mediated cell death.Cell death & disease · 2022Article
- Upregulation of miR-29c-3p Hinders Melanoma Progression by Inhibiting CDCA4 Expression.BioMed research international · 2021Article
- Countering TRAIL Resistance in Melanoma.Cancers · 2019Review
- MSC-Delivered Soluble TRAIL and Paclitaxel as Novel Combinatory Treatment for Pancreatic Adenocarcinoma.Theranostics · 2019Article
- Review
- Expansion of DUB functionality generated by alternative isoforms - USP35, a case study.Journal of cell science · 2018Article
- Kaempferol mitigates Endoplasmic Reticulum Stress Induced Cell Death by targeting caspase 3/7.Scientific reports · 2018Article
- XIAP underlies apoptosis resistance of renal cell carcinoma cells.Molecular medicine reports · 2018Article
- Systemic network analysis identifies XIAP and IκBα as potential drug targets in TRAIL resistant BRAF mutated melanoma.NPJ systems biology and applications · 2018Article
- A strategy for effective latent HIV reactivation using subtherapeutic drug doses.Scientific reports · 2017Article
- Emerging role of DUBs in tumor metastasis and apoptosis: Therapeutic implication.Pharmacology & therapeutics · 2017Review
- TRIM24 protein promotes and TRIM32 protein inhibits cardiomyocyte hypertrophy via regulation of dysbindin protein levels.The Journal of biological chemistry · 2017Article
- Article
- YClBioMed research international · 2017Article
- Embelin prevents LMP1-induced TRAIL resistance via inhibition of XIAP in nasopharyngeal carcinoma cells.Oncology letters · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Successful treatment of melanoma is still challenging, because metastasis remain chemoresistant and radioresistant. Accordingly, combinational treatments involving death ligands are mandatory. In a recent study from our lab, the majority out of 18 melanoma cell lines remained resistant against treatment with the death ligand TRAIL (tumor necrosis factor related apoptosis inducing ligand). Resistance was shown to be mainly due to incomplete processing of caspase-3 into catalytically inactive p21 by binding of the anti-apoptotic protein X-linked inhibitor of apoptosis protein (XIAP). Co-irradiation with sub-lethal ultraviolet (UV) B caused depletion of XIAP resulting in synergistic sensitization of all but two melanoma cell lines to TRAIL. We show here the XIAP depletion to essentially require initial caspase-mediated cleavage, which promotes proteasomal degradation of XIAP. Utilizing specific caspase inhibitors and small interfering RNA-mediated knockdown, we further identified caspase-3 to be responsible for performing the initial cleavage of XIAP after UVB treatment. Additional evidence suggests an accelerated mitochondrial outer membrane permeabilization in response to co-treatment with TRAIL and UVB, which directs the release of XIAP antagonizing factors including Smac. Distraction of XIAP consequently liberates caspase-3 to autocatalytically process into active p17. Activated caspase-3 cleaves XIAP and further enhances its activation in a positive regulatory feedback loop. The molecular mechanism discovered here appears to have broader implications, because cleavage of XIAP was also shown to accompany cisplatin-induced sensitization of melanoma cells to TRAIL.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.