ArticleOncotarget2014
Phospholipase D1 protein coordinates dynamic assembly of HIF-1α-PHD-VHL to regulate HIF-1α stability.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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.
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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
17 citing papers in PubMed, 22 citations in OpenAlex.
- Albiflorin-Mediated MAP2K1 Targeting and HIF-1 Signaling Inhibition Contribute to the Therapeutic Efficacy in Hyperuricemia-Associated Cognitive Impairment.Human mutation · 2026Article
- Short-Term: Cellular Metabolism and Gene Expression During the Onset of Diabetic Kidney Disease: A Diabetes Mellitus Experimental Model.International journal of molecular sciences · 2025Article
- Loss of VHL-mediated pRb regulation promotes clear cell renal cell carcinoma.Cell death & disease · 2025Article
- PLD1 is a key player in cancer stemness and chemoresistance: Therapeutic targeting of cross-talk between the PI3K/Akt and Wnt/β-catenin pathways.Experimental & molecular medicine · 2024Review
- Mitochondrial dysfunction induced by HIF-1α under hypoxia contributes to the development of gastric mucosal lesions.Clinical and translational medicine · 2024Article
- Phospholipase D2 is a positive regulator of sirtuin 1 and modulates p53-mediated apoptosis via sirtuin 1.Experimental & molecular medicine · 2021Article
- Hypoxia Pathway Proteins and Their Impact on the Blood Vasculature.International journal of molecular sciences · 2021Review
- Pleckstrin homology domain of phospholipase D2 is a negative regulator of focal adhesion kinase.BMB reports · 2021Article
- A compendium of proteins that interact with HIF-1α.Experimental cell research · 2017Article
- Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis.Journal of visualized experiments : JoVE · 2016Article
- Loss of PIG3 increases HIF-1α level by promoting protein synthesis via mTOR pathway in renal cell carcinoma cells.Oncotarget · 2016Article
- Article
- Wogonin inhibits multiple myeloma-stimulated angiogenesis via c-Myc/VHL/HIF-1α signaling axis.Oncotarget · 2016Article
- PHD2: from hypoxia regulation to disease progression.Hypoxia (Auckland, N.Z.) · 2016Review
- The pleckstrin homology domain of phospholipase D1 accelerates EGFR endocytosis by increasing the expression of the Rab5 effector, rabaptin-5.Experimental & molecular medicine · 2015Article
- Phospholipase D2 promotes degradation of hypoxia-inducible factor-1α independent of lipase activity.Experimental & molecular medicine · 2015Article
- Vitamin C inhibit the proliferation, migration and epithelial-mesenchymal-transition of lens epithelial cells by destabilizing HIF-1α.International journal of clinical and experimental medicine · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia-inducible factor-1α (HIF-1α) is a master transcriptional regulator of cellular response to hypoxia. In normoxia, HIF-1α is degraded through the prolyl hydroxylase (PHD) and von Hippel-Lindau (VHL) ubiquitination pathway. However, it is unknown whether PHD and VHL exert their enzymatic activities on HIF-1α separately or as a multiprotein complex. Here, we show that phospholipase D1 (PLD1) protein itself acts as a molecular platform, interacting directly with HIF-1α, PHD, and VHL, thereby dynamically assembling a multiprotein complex that mediates efficient degradation of HIF-1α in an O2-dependent manner. PLD1 depletion prevents degradation of HIF-1α; however, overall, PLD1 activity is predominantly involved in the upregulation of HIF-1α through increased translation, despite negative regulation of HIF-1α stability by PLD1 protein itself, suggesting dual roles of PLD1 in the regulation of HIF-1α. Disruption of the interactions of PLD1 with the proteins might be involved in hypoxic stabilization of HIF-1α. Interestingly, the pleckstrin homology domain interacting with these proteins promoted degradation of HIF-1α independent of oxygen concentration and suppressed tumor progression. These observations define a novel function of PLD1 as a previously unrecognized HIF-1α regulator.
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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.