ArticleMolecular cancer2015
Hypoxia inducible prolyl hydroxylase PHD3 maintains carcinoma cell growth by decreasing the stability of p27.
Article in Molecular cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- Endothelial prolyl hydroxylase 3 mitigates maladaptive inflammation to promote post-ischemic kidney repair.Kidney international · 2026Article
- Leukemia-expanded splenic CD81+ erythroblasts potentiate disease progression in mice by reshaping leukemic cell metabolism.The Journal of clinical investigation · 2025Article
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- LINC02774 inhibits glycolysis in glioma to destabilize HIF-1α dependent on transcription factor RP58.MedComm · 2023Article
- The multifaceted role of EGLN family prolyl hydroxylases in cancer: going beyond HIF regulation.Oncogene · 2022Review
- USP9X promotes apoptosis in cholangiocarcinoma by modulation expression of KIF1Bβ via deubiquitinating EGLN3.Journal of biomedical science · 2021Article
- Endogenous hydrogen sulfide regulates xCT stability through persulfidation of OTUB1 at cysteine 91 in colon cancer cells.Neoplasia (New York, N.Y.) · 2021Article
- Novel Small Molecule Hsp90/Cdc37 Interface Inhibitors Indirectly Target K-Ras-Signaling.Cancers · 2021Article
- mRNA overexpression of prolyl hydroxylase PHD3 is inversely related to nuclear grade in renal cell carcinoma.Molecular and clinical oncology · 2020Article
- Integrative -omics and HLA-ligandomics analysis to identify novel drug targets for ccRCC immunotherapy.Genome medicine · 2020Article
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- MAPKAPK2 plays a crucial role in the progression of head and neck squamous cell carcinoma by regulating transcript stability.Journal of experimental & clinical cancer research : CR · 2019Article
- Hypoxia-inducible factor (HIF)-prolyl hydroxylase 3 (PHD3) maintains highThe Journal of biological chemistry · 2019Article
- Prolyl 4-Hydroxylase Domain Protein 3-Inhibited Smooth-Muscle-Cell Dedifferentiation Improves Cardiac Perivascular Fibrosis Induced by Obstructive Sleep Apnea.BioMed research international · 2019Article
- Key miRNAs and target genes played roles in the development of clear cell renal cell carcinoma.Cancer biomarkers : section A of Disease markers · 2018Article
- Molecular Pathways: Hypoxia-Activated Prodrugs in Cancer Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Review
- Novel interactions of the von Hippel-Lindau (pVHL) tumor suppressor with the CDKN1 family of cell cycle inhibitors.Scientific reports · 2017Article
- HIF prolyl hydroxylase PHD3 regulates translational machinery and glucose metabolism in clear cell renal cell carcinoma.Cancer & metabolism · 2017Article
- The Expression of VHL (Von Hippel-Lindau) After Traumatic Spinal Cord Injury and Its Role in Neuronal Apoptosis.Neurochemical research · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHypoxia can halt cell cycle progression of several cell types at the G1/S interface. The arrest needs to be overcome by cancer cells. We have previously shown that the hypoxia-inducible cellular oxygen sensor PHD3/EGLN3 enhances hypoxic cell cycle entry at the G1/S boundary.
methodsWe used PHD3 knockdown by siRNA and shRNA in HeLa and 786-0 renal cancer cells. Flow cytometry with cell synchronization was used to study cell growth at different cell cycle phases. Total and phosphospecific antibodies together with cycloheximide chase were used to study p27/CDKN1B expression and fractionations for subcellular protein localization.
resultsHere we show that PHD3 enhances cell cycle by decreasing the expression of the CDK inhibitor p27/CDKN1B. PHD3 reduction led to increased p27 expression under hypoxia or VHL mutation. p27 was both required and sufficient for the PHD3 knockdown induced cell cycle block. PHD3 knockdown did not affect p27 transcription and the effect was HIF-independent. In contrast, PHD3 depletion increased the p27 half-life from G0 to S-phase. PHD3 depletion led to an increase in p27 phosphorylation at serine 10 without affecting threonine phosphorylation. Intact serine 10 was required for normal hypoxic and PHD3-mediated degradation of p27.
conclusionsThe data demonstrates that PHD3 can drive cell cycle entry at the G1/S transition through decreasing the half-life of p27 that occurs by attenuating p27S10 phosphorylation.
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