ArticleMolecular cancer therapeutics2008
Proteasome inhibitor PS-341 (VELCADE) induces stabilization of the TRAIL receptor DR5 mRNA through the 3'-untranslated region.
Article in Molecular cancer therapeutics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 41 citations in OpenAlex.
- Generation of TRAIL-resistant cell line models reveals distinct adaptive mechanisms for acquired resistance and re-sensitization.Oncogene · 2021Article
- Proteasome Inhibitors Suppress ErbB Family Expression through HSP90-Mediated Lysosomal Degradation.International journal of molecular sciences · 2019Article
- Pharmacological Targeting of Cell Cycle, Apoptotic and Cell Adhesion Signaling Pathways Implicated in Chemoresistance of Cancer Cells.International journal of molecular sciences · 2018Review
- Bortezomib-induced miRNAs direct epigenetic silencing of locus genes and trigger apoptosis in leukemia.Cell death & disease · 2017Article
- Intracellular localization of DR5 and related regulatory pathways as a mechanism of resistance to TRAIL in cancer.Cellular and molecular life sciences : CMLS · 2017Review
- Chloroquine enhances TRAIL-mediated apoptosis through up-regulation of DR5 by stabilization of mRNA and protein in cancer cells.Scientific reports · 2016Article
- Article
- Trailing TRAIL Resistance: Novel Targets for TRAIL Sensitization in Cancer Cells.Frontiers in oncology · 2015Review
- Rapid proteasomal degradation of posttranscriptional regulators of the TIS11/tristetraprolin family is induced by an intrinsically unstructured region independently of ubiquitination.Molecular and cellular biology · 2014Article
- DAPK2 is a novel modulator of TRAIL-induced apoptosis.Cell death and differentiation · 2014Article
- Regulation of TRAIL-receptor expression by the ubiquitin-proteasome system.International journal of molecular sciences · 2014Review
- HuR's post-transcriptional regulation of Death Receptor 5 in pancreatic cancer cells.Cancer biology & therapy · 2012Article
- Targeting the extrinsic apoptosis signaling pathway for cancer therapy.Cancer immunology, immunotherapy : CII · 2011Review
- Noxa/Bcl-2 protein interactions contribute to bortezomib resistance in human lymphoid cells.The Journal of biological chemistry · 2011Article
- Novel insights into the synergistic interaction of Bortezomib and TRAIL: tBid provides the link.Oncotarget · 2011Article
- Bortezomib sensitizes human renal cell carcinomas to TRAIL apoptosis through increased activation of caspase-8 in the death-inducing signaling complex.Molecular cancer research : MCR · 2010Article
- Quercetin enhances TRAIL-induced apoptosis in prostate cancer cells via increased protein stability of death receptor 5.Life sciences · 2010Article
- Proteasome inhibition and allogeneic hematopoietic stem cell transplantation: a review.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2009Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Addition of proteasome inhibitor PS-341 (VELCADE, bortezomib) to prostate cancer cells enhances cell death mediated by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). PS-341 sensitizes prostate cancer cells to TRAIL-induced apoptosis by increasing TRAIL receptors (DR5), inhibiting protein degradation, and elevating DR5 mRNA. Investigations into how PS-341 regulates the stability of DR5 mRNA revealed that PS-341 increased DR5 mRNA by extending its half-life from 4 to 10 h. The 2.5-kb 3'-untranslated region of the DR5 gene stabilized a heterologous gene in LNCaP human prostate cancer cells, suggesting the importance of this mRNA sequence. In contrast, human prostate cancer cell lines PC-3 and DU145 do not show this stabilization, suggesting cell specificity. PS-341 treatment of LNCaP cells increases the level of specific cytoplasmic mRNA-binding proteins, including AUF-1 isoforms, hnRNP C1/C2, and HuR proteins. In UV cross-linking experiments, after PS-341 treatment, the HuR protein markedly increases binding to specific sequences in the DR5 3'-untranslated region. In LNCaP cells treated with PS-341, small interfering RNA-mediated knockdown of HuR markedly decreases the half-life of DR5 mRNA, indicating that HuR is essential for mRNA stabilization. HuR protein is ubiquitinated, suggesting that PS-341 increases this protein by preventing its degradation. These experiments implicate modulation of mRNA stability as a novel mechanism by which proteasome inhibitors function, sensitizing cancer cells to antineoplastic agents.
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Registered trials
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