ArticleMolecules and cells2014
Hypoxia inducible factor-1α directly regulates nuclear clusterin transcription by interacting with hypoxia response elements in the clusterin promoter.
Article in Molecules and cells, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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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
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Links between the unfolded protein response and the DNA damage response in hypoxia: a systematic review.Biochemical Society transactions · 2021Pooled it
- Thirty Minutes of Hypobaric Hypoxia Provokes Alterations of Immune Response, Haemostasis, and Metabolism Proteins in Human Serum.International journal of molecular sciences · 2017Trial
- Clusterin: a double-edged sword in cancer and neurological disorders.EXCLI journal · 2024Review
- The role and function of CLU in cancer biology and therapy.Clinical and experimental medicine · 2023Review
- The Ins and Outs of Clusterin: Its Role in Cancer, Eye Diseases and Wound Healing.International journal of molecular sciences · 2023Review
- The Nuclear Transporter Importin 13 Can Regulate Stress-Induced Cell Death through the Clusterin/KU70 Axis.Cells · 2023Article
- A pan-cancer analysis reveals role of clusterin (Frontiers in genetics · 2022Article
- Contribution of the Transcription Factors Sp1/Sp3 and AP-1 toInternational journal of molecular sciences · 2021Article
- Proteotranscriptomic Measurements of E6-Associated Protein (E6AP) Targets in DU145 Prostate Cancer Cells.Molecular & cellular proteomics : MCP · 2018Article
- Divergent roles for Clusterin in Lung Injury and Repair.Scientific reports · 2017Article
- Proteomic profiling of the retinas in a neonatal rat model of oxygen-induced retinopathy with a reproducible ion-current-based MS1 approach.Journal of proteome research · 2015Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Differential transcription of the clusterin (CLU) gene yields two CLU isoforms, a nuclear form (nCLU) and a secretory form (sCLU), which play crucial roles in prostate tumorigenesis. Pro-apoptotic nCLU and anti-apoptotic sCLU have opposite effects and are differentially expressed in normal and cancer cells; however, their regulatory mechanisms at the transcriptional level are not yet known. Here, we examined the transcriptional regulation of nCLU in response to hypoxia. We identified three putative hypoxia response elements (HREs) in the human CLU promoter between positions -806 and +51 bp. Using a luciferase reporter, electrophoretic gel mobility shift, and chromatin immunoprecipitation assays, we further showed that hypoxia-inducible factor-1α (HIF-1α) bound directly to these sites and activated transcription. Exposure to the hypoxiamimetic compound CoCl₂, incubation under 1% O₂ conditions, or overexpression of HIF-1α enhanced nCLU expression and induced apoptosis in human prostate cancer PC3M cells. However, LNCaP prostate cancer cells were resistant to hypoxia-induced cell death. Methylation-specific PCR analysis revealed that the CLU promoter in PC3M cells was not methylated; in contrast, the CLU promoter in LNCap cells was methylated. Co-treatment of LNCaP cells with CoCl₂ and a demethylating agent promoted apoptotic cell death through the induction of nCLU. We conclude that nCLU expression is regulated by direct binding of HIF-1α to HRE sites and is epigenetically controlled by methylation of its promoter region.
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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.