ArticleThe Journal of clinical investigation2020
Parkin ubiquitinates phosphoglycerate dehydrogenase to suppress serine synthesis and tumor progression.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 92 citations in OpenAlex.
- PHGDH in cancer: a narrative review of its functions beyond serine metabolism.Translational cancer research · 2026Review
- Formation of tertiary lymphoid structures drives Parkin antitumor immunity.Science advances · 2026Article
- PRKN mediates the ubiquitination of SCAF8 to reduce the mRNA stability of KLF5 and its transcriptional activation of EFNA3 in colorectal cancer.Cellular & molecular biology letters · 2026Article
- PARP1-BCAT2 axis upregulates ABCG1 via histone lactylation to drive acquired PARP inhibitor resistance in prostate cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Targeting the noncanonical function of metabolic enzyme PHGDH in driving PD-L1 expression and cancer immune evasion.Cell reports. Medicine · 2026Article
- Integrative analysis and functional validation identified palmitoylated PHGDH as a therapeutic target for colon adenocarcinoma.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Post-translational regulation of human D-3-phosphoglycerate dehydrogenase in Alzheimer's disease.Protein science : a publication of the Protein Society · 2026Article
- PHGDH at the crossroads: metabolic plasticity, metastatic paradoxes, and therapeutic reconnaissance in cancer.Journal of biomedical science · 2026Review
- Molecular mechanism and potential role of mitophagy in breast cancer.Journal of Cancer · 2026Review
- The "serine code" of metabolic reprogramming: multidimensional roles of the serine synthesis pathway in tumors and novel breakthroughs for targeted therapy.Frontiers in immunology · 2026Review
- Therapeutic Promise of Mitophagy in Cancer: Advancing from Small-Molecule Regulation to Nanotechnology-Enhanced Targeting Therapy.Theranostics · 2026Review
- Integrative Bioinformatics Reveals Novel Molecular Mechanisms and Therapeutic Targets in Acute Myeloid Leukaemia.Journal of cellular and molecular medicine · 2026Article
- Parkin Induces Ubiquitination and Large Extracellular Vesicle Release of HMGB1 to Activate Antitumor Immunity.Cancer research · 2025Article
- Evaluation of Anticancer Potential ofAntioxidants (Basel, Switzerland) · 2025Article
- Review
- Mitophagy is responsible to ionizing radiation but plays a very limited role in the radiosensitivity of adenocarcinoma cells.Human cell · 2025Article
- Serine metabolism reprogramming in cancer: a multi-tiered regulatory framework.Acta biochimica et biophysica Sinica · 2025Review
- Protein post-translational modifications in serine synthetic pathway: functions and molecular mechanisms.Cell communication and signaling : CCS · 2025Review
- Serine auxotrophy is a targetable vulnerability driven by PSAT1 suppression in AML.bioRxiv : the preprint server for biology · 2025Article
- RFWD3 Reprograms Nucleotide Metabolism Through PHGDH to Induce Chemoresistance In Osteosarcoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
Phosphoglycerate dehydrogenase (PHGDH), the first rate-limiting enzyme of serine synthesis, is frequently overexpressed in human cancer. PHGDH overexpression activates serine synthesis to promote cancer progression. Currently, PHGDH regulation in normal cells and cancer is not well understood. Parkin, an E3 ubiquitin ligase involved in Parkinson's disease, is a tumor suppressor. Parkin expression is frequently downregulated in many types of cancer, and its tumor-suppressive mechanism is poorly defined. Here, we show that PHGDH is a substrate for Parkin-mediated ubiquitination and degradation. Parkin interacted with PHGDH and ubiquitinated PHGDH at lysine 330, leading to PHGDH degradation to suppress serine synthesis. Parkin deficiency in cancer cells stabilized PHGDH and activated serine synthesis to promote cell proliferation and tumorigenesis, which was largely abolished by targeting PHGDH with RNA interference, CRISPR/Cas9 KO, or small-molecule PHGDH inhibitors. Furthermore, Parkin expression was inversely correlated with PHGDH expression in human breast cancer and lung cancer. Our results revealed PHGDH ubiquitination by Parkin as a crucial mechanism for PHGDH regulation that contributes to the tumor-suppressive function of Parkin and identified Parkin downregulation as a critical mechanism underlying PHGDH overexpression in cancer.
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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.