ArticleScience signaling2013
A nontranscriptional role for HIF-1α as a direct inhibitor of DNA replication.
Article in Science signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
What it found
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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.
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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.
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Who cites it
76 citing papers in PubMed, 115 citations in OpenAlex.
- Progressive oxygenation of developing leaves directs morphogenesis.Science advances · 2026Article
- Dendritic cell-specific hypoxia-inducible factor-1α deficiency protects mice from recurrent retroviral infection.Experimental physiology · 2026Article
- HIF inhibition: Current strategies and clinical challenges.Redox biology · 2026Review
- Species, cell proliferation state and oxygen partial pressure are major factors in the in vitro toxicity of repurposed potential ADPKD drugs in human and murine renal proximal tubule cells.Archives of toxicology · 2026Article
- Global characterization of Dictyostelium discoideum gene and protein expression changes under hypoxic conditions.BMC genomics · 2025Article
- Hif-1 responsive IFFLs to explain specific transcriptional responses to cycling hypoxia in cancers.NPJ systems biology and applications · 2025Article
- Hypoxic reactivation of Kaposi's sarcoma associated herpesvirus.Cell insight · 2024Review
- A transcription-independent role for HIF-1α in modulating microprocessor assembly.Nucleic acids research · 2024Article
- Bhlhe40 Regulates Proliferation and Angiogenesis in Mouse Embryoid Bodies under Hypoxia.International journal of molecular sciences · 2024Article
- Lactate in breast cancer cells is associated with evasion of hypoxia-induced cell cycle arrest and adverse patient outcome.Human cell · 2024Article
- The MCM2-7 Complex: Roles beyond DNA Unwinding.Biology · 2024Review
- Combinatorial regulation by ERK1/2 and CK1δ protein kinases leads to HIF-1α association with microtubules and facilitates its symmetrical distribution during mitosis.Cellular and molecular life sciences : CMLS · 2024Article
- Hypoxia-inducible factor in cancer: from pathway regulation to therapeutic opportunity.BMJ oncology · 2024Review
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- Targeting hypoxia-inducible factor-1 alpha suppressesGut microbes · 2023Article
- Hypoxia induces a glycolytic complex in intestinal epithelial cells independent of HIF-1-driven glycolytic gene expression.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- A transient increase of HIF-1α during the G1 phase (G1-HIF) ensures cell survival under nutritional stress.Cell death & disease · 2023Article
- Lactate-dependent chaperone-mediated autophagy induces oscillatory HIF-1α activity promoting proliferation of hypoxic cells.Cell systems · 2022Article
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16 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
10 authors at 2 institutions in 1 country.
Funding
Abstract
Cell cycle arrest in response to hypoxia is a fundamental physiological mechanism to maintain a balance between O(2) supply and demand. Many of the cellular responses to reduced O(2) availability are mediated through the transcriptional activity of hypoxia-inducible factor 1 (HIF-1). We report a role for the isolated HIF-1α subunit as an inhibitor of DNA replication, and this role was independent of HIF-1β and transcriptional regulation. In response to hypoxia, HIF-1α bound to Cdc6, a protein that is essential for loading of the minichromosome maintenance (MCM) complex (which has DNA helicase activity) onto DNA, and promoted the interaction between Cdc6 and the MCM complex. Although the interaction between Cdc6 and the MCM complex increased the association of the MCM proteins with chromatin, the binding of HIF-1α to the complex decreased phosphorylation and activation of the MCM complex by the kinase Cdc7. As a result, HIF-1α inhibited firing of replication origins, decreased DNA replication, and induced cell cycle arrest in various cell types. These findings establish a transcription-independent mechanism by which the stabilization of HIF-1α leads to cell cycle arrest in response to hypoxia.
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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.