ArticleThe Journal of biological chemistry2019
Prolyl hydroxylase 3 stabilizes the p53 tumor suppressor by inhibiting the p53-MDM2 interaction in a hydroxylase-independent manner.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Oncometabolite 2-hydroxyglutarate destabilizes CDH1 to regulate quiescence and enhance chemotherapy sensitivity.Cell communication and signaling : CCS · 2026Article
- Endothelial prolyl hydroxylase 3 mitigates maladaptive inflammation to promote post-ischemic kidney repair.Kidney international · 2026Article
- PHD3 inhibits colon cancer cell metastasis through the occludin-p38 pathway.Acta biochimica et biophysica Sinica · 2023Article
- Proline hydroxylation of CREB-regulated transcriptional coactivator 2 controls hepatic glucose metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The multifaceted role of EGLN family prolyl hydroxylases in cancer: going beyond HIF regulation.Oncogene · 2022Review
- Morbid Obesity in Women Is Associated with an Altered Intestinal Expression of Genes Related to Cancer Risk and Immune, Defensive, and Antimicrobial Response.Biomedicines · 2022Article
- Inactivation of EGLN3 hydroxylase facilitates Erk3 degradation via autophagy and impedes lung cancer growth.Oncogene · 2022Article
- Targeting Post-Translational Regulation of p53 in Colorectal Cancer by Exploiting Vulnerabilities in the p53-MDM2 Axis.Cancers · 2022Review
- EGLN1 induces tumorigenesis and radioresistance in nasopharyngeal carcinoma by promoting ubiquitination of p53 in a hydroxylase-dependent manner.Journal of Cancer · 2022Article
- Proline oxidase silencing inhibits p53-dependent apoptosis in MCF-7 breast cancer cells.Amino acids · 2021Article
- Understanding the Oxygen-Sensing Pathway and Its Therapeutic Implications in Diseases.The American journal of pathology · 2020Review
- Prolyl hydroxylase 3 controls the intestine goblet cell generation through stabilizing ATOH1.Cell death and differentiation · 2020Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Prolyl hydroxylase 3 (PHD3) has initially been reported to hydroxylase hypoxia-inducible factor α (HIFα) and mediate HIFα degradation. More recent studies have shown that, in addition to HIFα, PHD3 has also other substrates. Moreover, pHD3 is believed to act as a tumor suppressor, but the underlying mechanism remains to be elucidated. Here, we demonstrate that PHD3 stabilizes p53 in a hydroxylase-independent manner. We found that PHD3 overexpression increases and PHD3 knockdown decreases p53 levels. Mechanistically, PHD3 bound MDM2 proto-oncogene (MDM2) and prevented MDM2 from interacting with p53, thereby inhibiting MDM2-mediated p53 degradation. Interestingly, we found that PHD3 overexpression could enhance p53 in the presence of the prolyl hydroxylase inhibitor dimethyloxalylglycine, and the prolyl hydroxylase activity-deficient variant PHD3-H196A also inhibited the p53-MDM2 interaction and stabilized p53. Genetic ablation of PHD3 decreased p53 protein levels in mice intestinal epithelial cells, but a genetic knockin of PHD3-H196A did not affect p53 protein levels
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