ArticleNature communications2017
Parkin targets HIF-1α for ubiquitination and degradation to inhibit breast tumor progression.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
140 citing papers in PubMed, 2 syntheses or guidelines pooled it, 205 citations in OpenAlex.
- Risk of colorectal cancer in Parkinson's disease: a systematic review and meta-analysis of 11 million participants.BMC neurology · 2025Pooled it
- E3 Ubiquitin Ligases in Breast Cancer Metastasis: A Systematic Review of Pathogenic Functions and Clinical Implications.Frontiers in oncology · 2021Pooled it
- Decoding Mitophagy in Breast Cancer: Biological Mechanisms, Dual Roles, and Clinical Implications.Cells · 2026Review
- Lysyl oxidase inhibition disrupts mitochondrial homeostasis to create vulnerability to ferroptosis in TNBC.Cell reports. Medicine · 2026Article
- Post-translational modifications in Neuroimmune cells during neuroinflammation: integrated regulatory networks and therapeutic opportunities.Biology direct · 2026Review
- A non-canonical function of RNF8 opposes TRAF6-mediated stabilization of HIF1α.RSC chemical biology · 2026Article
- A feedback mechanism between E3 ligase RNF122 and HIF-1α inhibits aggressive behavior in breast cancer.Oncogene · 2026Article
- Characterizing the Mutational Landscape of In-Transit Melanoma Metastases.Pigment cell & melanoma research · 2026Article
- PARK2 Inhibits the progression of colorectal cancer via ubiquitinating MARCKSL1 to inhibit the c-Myc pathway.Cellular and molecular life sciences : CMLS · 2026Article
- p53: from understanding its structure to advances in therapeutic targeting.Signal transduction and targeted therapy · 2026Review
- Parkin-mediated ubiquitination of hif-α modulates hypoxia signaling in Megalobrama amblycephala.BMC genomics · 2026Article
- Mitophagy and Ubiquitination Coordinate Context-Specific Mitochondrial Quality Control and EMT/MET Plasticity to Drive Cancer Cell Invasion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Targeting aerobic glycolysis combats tyrosine kinase inhibitor resistance of hepatocellular carcinoma.International journal of cancer · 2026Review
- Mitophagy in the pathogenesis and management of disease.Cell research · 2026Review
- Mitochondrial quality control mechanisms as molecular targets for impaired lung development: from fetuses to neonates.Respiratory research · 2025Review
- The multifaceted role of E3 ubiquitin ligases in cancer metastasis: mechanisms, targets, and therapeutic implications.Essays in biochemistry · 2025Review
- Parkin Induces Ubiquitination and Large Extracellular Vesicle Release of HMGB1 to Activate Antitumor Immunity.Cancer research · 2025Article
- Review
- USP13 promotes colorectal cancer progression by deubiquitinating and stabilizing HIF-1α.Cell communication and signaling : CCS · 2025Article
- CHCHD2 mutant mice link mitochondrial deficits to PD pathophysiology.Science advances · 2025Article
80 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
Mutations in E3 ubiquitin ligase Parkin have been linked to familial Parkinson's disease. Accumulating evidence suggests that Parkin is a tumor suppressor, but the underlying mechanism is poorly understood. Here we show that Parkin is an E3 ubiquitin ligase for hypoxia-inducible factor 1α (HIF-1α). Parkin interacts with HIF-1α and promotes HIF-1α degradation through ubiquitination, which in turn inhibits metastasis of breast cancer cells. Parkin downregulation in breast cancer cells promotes metastasis, which can be inhibited by targeting HIF-1α with RNA interference or the small-molecule inhibitor YC-1. We further identify lysine 477 (K477) of HIF-1α as a major ubiquitination site for Parkin. K477R HIF-1α mutation and specific cancer-associated Parkin mutations largely abolish the functions of Parkin to ubiquitinate HIF-1α and inhibit cancer metastasis. Importantly, Parkin expression is inversely correlated with HIF-1α expression and metastasis in breast cancer. Our results reveal an important mechanism for Parkin in tumor suppression and HIF-1α regulation.
Indexed as
Identifiers
What OpenQuestion holds
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.