ArticleNature2017
Hypersensitive termination of the hypoxic response by a disordered protein switch.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 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
111 citing papers in PubMed, 171 citations in OpenAlex.
- Article
- Current Challenges of Transcription Compartmentalization Research.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Sequence-encoded differences in the conformational ensembles of CITED transcriptional activation domains impact coactivator binding.Protein science : a publication of the Protein Society · 2026Article
- Dynamic control of IDP interaction network via diverse binding pathways.Nature communications · 2026Article
- 14-3-3ζ interacts with DNA-binding domain of FOXO3a and competitively dissociates DNA by dual-motif tethering.Nature communications · 2026Article
- Sequence-encoded differences in the conformational ensembles of CITED transcriptional activation domains impact coactivator binding.bioRxiv : the preprint server for biology · 2026Article
- Article
- Integrative skin-blood transcriptomic analysis identifies circulating biomarkers reflecting disease activity in atopic dermatitis.Frontiers in allergy · 2026Article
- Digital Twin Meets the Bench: Natural Compounds Reshape the Ovarian Cancer Microenvironment.Biomedicines · 2025Article
- Linker Length and Composition within Disordered Binding Motifs Modulates the Avidity and Reversibility of a Multivalent Protein Interaction Switch.Journal of molecular biology · 2025Article
- The BRD4-nucleosome interaction is enhanced modestly and non-selectively by histone acetylation.Nucleic acids research · 2025Article
- Super-Enhancer Target Gene CBP/p300-Interacting Transactivator With Glu/Asp-Rich C-Terminal Domain, 2 Cooperates With Transcription Factor Forkhead Box J3 to Inhibit Pulmonary Vascular Remodeling.Cell proliferation · 2025Article
- Article
- Transient non-local interactions dominate the dynamics of measles virus NCommunications chemistry · 2025Article
- Short activation domains control chromatin association of transcription factors.bioRxiv : the preprint server for biology · 2025Article
- Hierarchy in regulator interactions with distant transcriptional activation domains empowers rheostatic regulation.Protein science : a publication of the Protein Society · 2025Article
- Decoding Order and Disorder in Proteins by NMR Spectroscopy.Journal of the American Chemical Society · 2025Article
- CITED2 is highly-expressed and PRX4 is poorly-expressed in preeclampsia and have diagnostic values.Journal of human hypertension · 2025Article
- Acteoside ameliorates hepatocyte ferroptosis and hepatic ischemia-reperfusion injuryActa pharmaceutica Sinica. B · 2025Article
- Dynamic interactions of dimeric hub proteins underlie their diverse functions and structures: A comparative analysis of 14-3-3 and LC8.The Journal of biological chemistry · 2025Review
51 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The cellular response to hypoxia is critical for cell survival and is fine-tuned to allow cells to recover from hypoxic stress and adapt to heterogeneous or fluctuating oxygen levels. The hypoxic response is mediated by the α-subunit of the transcription factor HIF-1 (HIF-1α), which interacts through its intrinsically disordered C-terminal transactivation domain with the TAZ1 (also known as CH1) domain of the general transcriptional coactivators CBP and p300 to control the transcription of critical adaptive genes. One such gene encodes CITED2, a negative feedback regulator that attenuates HIF-1 transcriptional activity by competing for TAZ1 binding through its own disordered transactivation domain. Little is known about the molecular mechanism by which CITED2 displaces the tightly bound HIF-1α from their common cellular target. The HIF-1α and CITED2 transactivation domains bind to TAZ1 through helical motifs that flank a conserved LP(Q/E)L sequence that is essential for negative feedback regulation. Here we show that human CITED2 displaces HIF-1α by forming a transient ternary complex with TAZ1 and HIF-1α and competing for a shared binding site through its LPEL motif, thus promoting a conformational change in TAZ1 that increases the rate of HIF-1α dissociation. Through allosteric enhancement of HIF-1α release, CITED2 activates a highly responsive negative feedback circuit that rapidly and efficiently attenuates the hypoxic response, even at modest CITED2 concentrations. This hypersensitive regulatory switch is entirely dependent on the unique flexibility and binding properties of these intrinsically disordered proteins and probably exemplifies a common strategy used by the cell to respond rapidly to environmental signals.
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.