ArticleNature2016
An ID2-dependent mechanism for VHL inactivation in cancer.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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
85 citing papers in PubMed, 127 citations in OpenAlex.
- CDK6/4 inactivates BAP1 deubiquitinase destabilizing VHL to promote metastatic colonization in liver.Molecular cancer · 2026Article
- Machine learning-predicted chromatin organization landscape across pediatric tumors.Scientific reports · 2026Article
- Redox-Amino Acid Metabolic Crosstalk in Ovarian Cancer Stem Cells: Integrating Metabolic Reprogramming, Signaling, and the Tumor Microenvironment.Antioxidants (Basel, Switzerland) · 2025Review
- Von Hippel-Lindau/Hypoxia Inducible Factor Axis in Glioblastoma.International journal of molecular sciences · 2025Review
- Chronic cerebral hypoperfusion induces venous dysfunction via EPAS1 regulation in mice.Nature communications · 2025Article
- DYRK1B phosphorylates FOXO1 to promote hepatic gluconeogenesis.Nucleic acids research · 2025Article
- Id2 exacerbates the development of rheumatoid arthritis by increasing IFN-γ production in CD4Clinical and translational medicine · 2025Article
- ID2 promotes tumor progression and metastasis in thyroid cancer.Endocrine · 2024Article
- Mirk/Dyrk1B Kinase Inhibitors in Targeted Cancer Therapy.Pharmaceutics · 2024Review
- Regulation of CMGC kinases by hypoxia.BMB reports · 2023Review
- Identification of Maleimide-Fused Carbazoles as Novel Noncanonical Bone Morphogenetic Protein Synergizers.ACS pharmacology & translational science · 2023Article
- ER chaperone GRP78/BiP translocates to the nucleus under stress and acts as a transcriptional regulator.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- DYRK1A-mediated PLK2 phosphorylation regulates the proliferation and invasion of glioblastoma cells.International journal of oncology · 2023Article
- Review
- Insights from the protein interaction Universe of the multifunctional "Goldilocks" kinase DYRK1A.Frontiers in cell and developmental biology · 2023Review
- Pointing fingers at blood contact: mechanisms of subventricular zone neural stem cell differentiation.Neural regeneration research · 2023Article
- The Omnipresence of DYRK1A in Human Diseases.International journal of molecular sciences · 2022Review
- ID2 and HIF-1α collaborate to protect quiescent hematopoietic stem cells from activation, differentiation, and exhaustion.The Journal of clinical investigation · 2022Article
- MiR-1248: a new prognostic biomarker able to identify supratentorial hemispheric pediatric low-grade gliomas patients associated with progression.Biomarker research · 2022Article
- DYRK1A reinforces epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma via cooperatively activating STAT3 and SMAD.Journal of biomedical science · 2022Article
25 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
12 authors at 3 institutions in 1 country.
Funding
Abstract
Mechanisms that maintain cancer stem cells are crucial to tumour progression. The ID2 protein supports cancer hallmarks including the cancer stem cell state. HIFα transcription factors, most notably HIF2α (also known as EPAS1), are expressed in and required for maintenance of cancer stem cells (CSCs). However, the pathways that are engaged by ID2 or drive HIF2α accumulation in CSCs have remained unclear. Here we report that DYRK1A and DYRK1B kinases phosphorylate ID2 on threonine 27 (Thr27). Hypoxia downregulates this phosphorylation via inactivation of DYRK1A and DYRK1B. The activity of these kinases is stimulated in normoxia by the oxygen-sensing prolyl hydroxylase PHD1 (also known as EGLN2). ID2 binds to the VHL ubiquitin ligase complex, displaces VHL-associated Cullin 2, and impairs HIF2α ubiquitylation and degradation. Phosphorylation of Thr27 of ID2 by DYRK1 blocks ID2-VHL interaction and preserves HIF2α ubiquitylation. In glioblastoma, ID2 positively modulates HIF2α activity. Conversely, elevated expression of DYRK1 phosphorylates Thr27 of ID2, leading to HIF2α destabilization, loss of glioma stemness, inhibition of tumour growth, and a more favourable outcome for patients with glioblastoma.
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.