ArticleMolecular and cellular biology2006
The proteasome is required for rapid initiation of death receptor-induced apoptosis.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 39 citations in OpenAlex.
- Proteasome Inhibitor-Induced Cytotoxic Mechanisms in Canine Pulmonary Adenocarcinoma Cell Lines.Veterinary and comparative oncology · 2026Article
- Combined inhibition of class 1-PI3K-alpha and delta isoforms causes senolysis by inducing p21Cell death & disease · 2024Article
- Proteasome complexes experience profound structural and functional rearrangements throughout mammalian spermatogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Identification ofOncology letters · 2021Article
- Tumor necrosis factor related apoptosis inducing ligand (TRAIL) regulates deubiquitinase USP5 in tumor cells.Oncotarget · 2019Article
- The prodomain of caspase-3 regulates its own removal and caspase activation.Cell death discovery · 2019Article
- Linear ubiquitination of cFLIP induced by LUBAC contributes to TNFα-induced apoptosis.The Journal of biological chemistry · 2018Article
- Stress-induced endocytosis and degradation of epidermal growth factor receptor are two independent processes.Cancer cell international · 2016Article
- Oppositional regulation of Noxa by JNK1 and JNK2 during apoptosis induced by proteasomal inhibitors.PloS one · 2013Article
- Proteasome inhibition can impair caspase-8 activation upon submaximal stimulation of apoptotic tumor necrosis factor-related apoptosis inducing ligand (TRAIL) signaling.The Journal of biological chemistry · 2012Article
- Caspase-3 cleaves XIAP in a positive feedback loop to sensitize melanoma cells to TRAIL-induced apoptosis.Oncogene · 2011Article
- Stabilization of XIAP mRNA through the RNA binding protein HuR regulated by cellular polyamines.Nucleic acids research · 2009Article
- Article
- Sensitization of melanoma cells to TRAIL by UVB-induced and NF-kappaB-mediated downregulation of xIAP.Oncogene · 2009Article
- Proteasome inhibition improves diaphragm function in congestive heart failure rats.American journal of physiology. Lung cellular and molecular physiology · 2008Article
- Killing of macrophages by anthrax lethal toxin: involvement of the N-end rule pathway.Cellular microbiology · 2008Article
- Inhibition of ubiquitin-mediated degradation of MOAP-1 by apoptotic stimuli promotes Bax function in mitochondria.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
- Notch inhibits apoptosis by direct interference with XIAP ubiquitination and degradation.The EMBO journal · 2007Article
- CD95 ligand mediates T-cell receptor-induced apoptosis of a CD4+ CD8+ double positive thymic lymphoma.Oncogene · 2006Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Due to their tremendous apoptosis-inducing potential, proteasomal inhibitors (PIs) have recently entered clinical trials. Here we show, however, that various PIs rescued proliferating tumor cells from death receptor-induced apoptosis. This protection correlated with the stabilization of X-linked IAP (XIAP) and c-FLIP and the inhibition of caspase activation. Together with the observation that PIs could not protect cells expressing XIAP or c-FLIP short interfering RNAs (siRNAs) from death receptor-induced apoptosis, our results demonstrate that PIs mediate their protective effect via the stabilization of these antiapoptotic proteins. Furthermore, we 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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Registered trials
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.