Affinage

HIF1A

Hypoxia-inducible factor 1-alpha · UniProt Q16665

Length
826 aa
Mass
92.7 kDa
Annotated
2026-06-10
100 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HIF-1α is the master oxygen-sensitive bHLH-PAS transcription factor that reprograms cellular physiology in response to hypoxia (PMID:17925579, PMID:19942427). Under normoxia its stability and activity are controlled by O2-dependent dioxygenases: PHD2 hydroxylates P402/P564 to license VHL-mediated ubiquitination and proteasomal degradation, while FIH-1 hydroxylates N803 to block recruitment of the p300/CBP coactivator, both using O2 and α-ketoglutarate as cosubstrates (PMID:17925579). Beyond this canonical axis, HIF-1α abundance is set by O2-independent inputs that converge on the same ubiquitin machinery: RACK1 competes with HSP90 for the PAS-A domain and recruits the Elongin-B/C ligase to drive degradation (PMID:17361105), whereas the deubiquitylases USP51 (acting within a VHL/CUL2/ELOB/ELOC complex regulated by SENP1-dependent deSUMOylation of ELOC) and BAP1 remove ubiquitin to stabilize HIF-1α (PMID:37816999, PMID:36656861); PADI4-mediated citrullination at R698 stabilizes the protein by blocking VHL binding (PMID:39227578), and inflammatory signaling through IKKβ raises HIF-1α protein without changing its mRNA (PMID:19766100). HIF1A expression is additionally gated epigenetically, with KDM4-family histone demethylases removing repressive H3K9me3 at the locus—an axis that distinguishes intermittent from chronic hypoxia—and STAT1 acting as a transcriptional repressor of the promoter (PMID:28894274, PMID:36174675, PMID:36300763). Once stabilized and dimerized, HIF-1α binds hypoxia response elements to activate a metabolic and angiogenic program, inducing PDK1 and BNIP3 to shift cells from oxidative phosphorylation to glycolysis (PMID:19942427) and driving targets including VEGF, S100A8/A9, WASF3, and CYP19A1 (PMID:11707426, PMID:22505354, PMID:22581642, PMID:32127571). Its transcriptional output is shaped combinatorially by partner factors—PER2 facilitates HRE recruitment, p53 acts as a chaperone stabilizing HIF-1α at HREs, CARM1 co-occupies target promoters, Sp1 switches HIF-1α onto the MutSα mismatch-repair genes to repress them, and OLIG2 redirects HIF-1α to non-canonical targets in oligodendrocyte progenitors (PMID:28963769, PMID:31538203, PMID:38476024, PMID:15780936, PMID:33091368). Physiologically, HIF-1α enforces tissue-specific outcomes, suppressing mitochondrial biogenesis in skeletal muscle (PMID:18269201), limiting post-ischemic cardiac fibroblast proliferation by controlling mitochondrial ROS (PMID:34762860), and supporting macrophage autophagy-dependent antibacterial defense (PMID:30982460).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2001 Medium

    Identifying Jab1 as a direct HIF-1α partner showed that protein-protein interactions, not just oxygen chemistry, govern HIF-1α stability and activity.

    Evidence Yeast two-hybrid, GST pulldown, Co-IP and reporter assays in HEK293 cells

    PMID:11707426

    Open questions at the time
    • Structural basis of the Jab1-HIF-1α interface not defined
    • Whether Jab1 acts via the COP9 signalosome in this context untested
  2. 2005 High

    Demonstrating that HIF-1α displaces Myc at Sp1 sites to repress MutSα genes established HIF-1α as a context-dependent transcriptional repressor causing genetic instability, not only an activator.

    Evidence ChIP, reporter and gel-shift assays, siRNA, p53-dependence epistasis in colon cancer cells and patient specimens

    PMID:15780936

    Open questions at the time
    • Generality of the Sp1 switch to other promoters unknown
    • Direct vs indirect role of p53 in repression not fully resolved
  3. 2007 High

    Dissection of PHD2/VHL and FIH-1 hydroxylation reactions defined the dual O2-dependent control of HIF-1α stability and coactivator recruitment, the foundational oxygen-sensing mechanism.

    Evidence Enzymatic assays and mutagenesis synthesized in pathway review

    PMID:17925579

    Open questions at the time
    • Quantitative O2 thresholds for each hydroxylase in vivo not specified
    • Crosstalk between the two hydroxylation events under graded hypoxia
  4. 2007 High

    Showing RACK1 competes with HSP90 and recruits Elongin-B/C established an O2/PHD/VHL-independent route to HIF-1α degradation, expanding stability control beyond the hydroxylase axis.

    Evidence Reciprocal Co-IP, domain mapping, ubiquitination and proteasome-inhibitor assays

    PMID:17361105

    Open questions at the time
    • Physiological signals that tip the HSP90/RACK1 balance unclear
    • Tissue contexts where this pathway dominates not defined
  5. 2009 Medium

    Linking TNFα/IKKβ to HIF-1α protein accumulation connected inflammatory signaling to HIF-1α independent of transcription, broadening its regulatory inputs.

    Evidence Western blot, overexpression, siRNA, pharmacological inhibition and IKKβ-KO MEFs

    PMID:19766100

    Open questions at the time
    • Molecular step by which IKKβ raises HIF-1α protein not identified
    • Whether degradation or translation is targeted unresolved
  6. 2009 Medium

    Tissue-specific knockouts revealed HIF-1α as a physiological brake on oxidative metabolism in skeletal muscle and a coordinator of the glycolytic switch via PDK1 and BNIP3.

    Evidence Skeletal-muscle Hif1a KO mice with metabolic phenotyping; transcriptional target analysis of PDK1/BNIP3

    PMID:18269201 PMID:19942427

    Open questions at the time
    • Relative contribution of individual targets to the metabolic phenotype unclear
    • Cross-tissue generality of the metabolic brake untested
  7. 2012 Medium

    ChIP-validated direct targets S100A8/A9 and WASF3 connected HIF-1α transcriptional activity to invasion and motility programs in cancer cells.

    Evidence ChIP, reporter assays, siRNA knockdown, motility assays under hypoxia

    PMID:22505354 PMID:22581642

    Open questions at the time
    • Contribution relative to other invasion targets not quantified
    • In vivo metastasis dependence not established
  8. 2017 Medium

    Defining KDM4A-mediated H3K9me3 removal at the HIF1A locus established epigenetic control of HIF1A transcription as a distinct regulatory layer.

    Evidence KDM4A siRNA, H3K9me3 ChIP at HIF1A, RT-qPCR, invasion/migration assays

    PMID:28894274

    Open questions at the time
    • Upstream signals controlling KDM4A activity at this locus unknown
    • Single-lab observation
  9. 2017 Medium

    Identifying PER2 as an effector that recruits HIF-1α to HREs tied circadian machinery to hypoxic transcription and linked it mechanistically to N803 hydroxylation status.

    Evidence Reciprocal Co-IP, ChIP, HRE reporter, N803A mutation and FIH inhibition

    PMID:28963769

    Open questions at the time
    • Whether PER2 acts on canonical or specific subsets of HREs unclear
    • Circadian timing of the effect not directly tested
  10. 2019 Medium

    p53 was shown to act both as a HIF-1α transcriptional target and as a chaperone stabilizing HIF-1α at HREs, revealing reciprocal HIF-1α/p53 regulation.

    Evidence ChIP, luciferase reporter, Co-IP, protein-DNA binding, siRNA

    PMID:31538203

    Open questions at the time
    • Mechanism by which transcriptionally inactive p53 stabilizes DNA binding unclear
    • In vivo relevance of the feed-forward loop untested
  11. 2019 Medium

    Genetic dissection placed HIF1A within macrophage salt-boosted antibacterial defense and identified STAT1 as a transcriptional repressor of HIF1A controlling angiogenesis.

    Evidence Conditional/EC-specific KO mice, ChIP, autophagy/lysosomal assays, HIF1A overexpression rescue

    PMID:30982460 PMID:36300763

    Open questions at the time
    • Direct HIF-1α target genes in the antibacterial program not all defined
    • STAT1 repression generality across tissues unknown
  12. 2021 High

    Cell-type-specific studies established HIF-1α as a protective brake on cardiac fibroblast proliferation via mitochondrial ROS control and as a driver of non-canonical, OLIG2-dependent transcription blocking oligodendrocyte differentiation.

    Evidence Conditional Hif1a KO, scRNA-seq, ChIP-seq, MitoTEMPO rescue, MEK/ERK inhibitor rescue, spheroid models

    PMID:33091368 PMID:34762860

    Open questions at the time
    • How HIF-1α selects non-canonical vs canonical targets mechanistically unresolved
    • ROS target genes mediating the fibroblast brake not enumerated
  13. 2023 High

    Discovery of USP51 and BAP1 as HIF-1α deubiquitylases established active deubiquitylation, including a SENP1/SUMO-regulated USP51 feedback loop, as a positive arm of HIF-1α stability control.

    Evidence Co-IP of complexes, in vitro deubiquitination, ChIP, ELOC K32 and BAP1 interaction-domain mutagenesis, patient IHC

    PMID:36656861 PMID:37816999

    Open questions at the time
    • Relative contribution of USP51 vs BAP1 across cell types unclear
    • Conditions activating each DUB physiologically not defined
  14. 2024 High

    Identification of PADI4-mediated R698 citrullination as a VHL-blocking modification, and CARM1 as a recruited co-regulator on shared promoters, extended the post-translational and cofactor repertoire controlling HIF-1α.

    Evidence In vitro citrullination, Co-IP, R698 mutagenesis, VHL/ubiquitination assays; CARM1 Co-IP and ChIP-seq with functional knockdown

    PMID:38476024 PMID:39227578

    Open questions at the time
    • Signals controlling PADI4 recruitment to HIF-1α unknown
    • Whether CARM1 methylates HIF-1α directly not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many parallel stability inputs (hydroxylation, RACK1, DUBs, citrullination, IKKβ) and combinatorial cofactors are integrated to set context-specific HIF-1α target selection remains unresolved.
  • No unified quantitative model linking competing stability pathways
  • Determinants of canonical vs non-canonical target choice undefined
  • Structural basis of most HIF-1α cofactor interfaces unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 3
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1430728 Metabolism 2 R-HSA-8953897 Cellular responses to stimuli 2
Partners
BAP1FIH1PADI4PER2PHD2RACK1USP51VHL

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 HIF-1α is hydroxylated at proline residues 402 and/or 564 by PHD2 (prolyl hydroxylase domain protein 2), promoting binding of the von Hippel-Lindau protein (VHL), leading to ubiquitination and proteasomal degradation. HIF-1α is also hydroxylated at asparagine residue 803 by FIH-1 (factor inhibiting HIF-1), blocking binding of the p300/CBP coactivator. Both hydroxylation reactions utilize O2 and alpha-ketoglutarate as substrates. Biochemical pathway dissection; enzymatic assays; mutagenesis studies synthesized in pathway review Science's STKE High 17925579
2007 RACK1 competes with HSP90 for binding to the PAS-A domain of HIF-1α and promotes O2/PHD/VHL-independent, proteasome-dependent degradation of HIF-1α by binding Elongin-C and recruiting the Elongin-B/C E3 ubiquitin ligase complex to HIF-1α. Co-immunoprecipitation, domain-mapping pulldown, ubiquitination assay, proteasome inhibitor experiments Cell cycle (Georgetown, Tex.) High 17361105
2001 Jab1 (Jun activation domain-binding protein 1, fifth subunit of COP9 signalosome) directly interacts with HIF-1α, increases HIF-1α protein stability, enhances HIF-1 transcriptional activity under hypoxia (increasing VEGF expression), and interferes with the binding of p53 to HIF-1α in a Jab1-dependent manner. Yeast two-hybrid screening, GST pull-down assay, co-immunoprecipitation in HEK 293 cells, reporter assay The Journal of biological chemistry Medium 11707426
2005 HIF-1α represses expression of MSH2 and MSH6 (the MutSα mismatch repair complex) by displacing the transcriptional activator Myc from Sp1 binding sites at MutSα gene promoters; Sp1 serves as a molecular switch recruiting HIF-1α to the promoter under hypoxia. This is p53-dependent and causes nucleotide-level genetic instability. Reporter assays, ChIP, siRNA knockdown, gel-shift assays, genetic analysis of human colon cancer specimens Molecular cell High 15780936
2019 HIF-1α transcriptionally upregulates p53 (both WT and MT) by binding to five response elements in the p53 promoter under hypoxia. The resulting hypoxia-induced p53 protein (transcriptionally inactive) acts as a chaperone, binding HIF-1α and stabilizing its association with downstream DNA response elements (HREs), thereby increasing HIF-1α-regulated gene synthesis. ChIP, luciferase reporter assay, co-immunoprecipitation, protein-DNA binding assays, siRNA knockdown Nucleic acids research Medium 31538203
2009 TNFα induces HIF-1α protein accumulation (without affecting HIF-1α mRNA) in an IKKβ-dependent manner. IKKβ overexpression increases HIF-1α protein, and IKKβ inhibition or knockout reduces TNFα-induced HIF-1α and VEGF expression. Western blot, stable transfection, siRNA knockdown, pharmacological inhibition (Bay 11-7082), MEF IKKβ knockout cells Biochemical and biophysical research communications Medium 19766100
2017 The histone demethylase KDM4A controls HIF-1α levels by removing the repressive H3K9me3 mark at the HIF1A locus; KDM4A depletion or inactivation causes H3K9me3 accumulation at the HIF1A locus, decreasing HIF-1α mRNA and protein, and reduces hypoxia-driven invasion, migration, and oxygen consumption. KDM4A siRNA knockdown, ChIP for H3K9me3 at HIF1A locus, RT-qPCR, invasion/migration assays Scientific reports Medium 28894274
2022 Intermittent hypoxia (minutes) increases HIF-1α protein through a distinct pathway from chronic hypoxia: KDM4A, KDM4B, and KDM4C histone demethylases are activated by intermittent hypoxia, removing H3K9me3 at the HIF1A locus and increasing HIF1A mRNA. Chronic hypoxia conversely decreases KDM4A/B/C activity, leading to H3K9me3 hypertrimethylation at the HIF1A locus. H3K9me3 ChIP at HIF1A locus, RT-qPCR, KDM4A/B/C inhibition and depletion, protein activity assays The Journal of biological chemistry Medium 36174675
2024 PADI4 directly interacts with HIF-1α and citrullinates it at arginine R698. This citrullination blocks VHL binding to HIF-1α, thereby antagonizing HIF-1α ubiquitination and proteasomal degradation, stabilizing HIF-1α. Co-immunoprecipitation, in vitro citrullination assay, site-directed mutagenesis (R698), VHL binding assay, ubiquitination assay Nature communications High 39227578
2023 USP51 forms a complex with VHL E3 ligase components (USP51/VHL/CUL2/ELOB/ELOC/RBX1) and directly deubiquitinates HIF-1α, stabilizing it and activating hypoxia-induced gene transcription. Conversely, HIF-1α transcriptionally upregulates USP51, forming a positive feedback loop. SUMOylation of ELOC at K32 inhibits USP51 binding; SENP1-mediated deSUMOylation of ELOC promotes USP51-ELOC interaction and HIF-1α deubiquitination. Co-immunoprecipitation, in vitro deubiquitination assay, ChIP, reporter assay, site-directed mutagenesis (ELOC K32), SUMO assay Cell death and differentiation High 37816999
2023 BAP1 (BRCA1-associated protein 1) binds HIF-1α during hypoxia, deubiquitylates it, and stabilizes it. BAP1 interacts with the N-terminal region of HIF-1α (where HIF-1α binds DNA and dimerizes with HIF-1β). Mutations of BAP1 residues I675, F678, I679, and L691 abolish interaction with HIF-1α. Loss of BAP1 reduces nuclear HIF-1α levels in hypoxia. Co-immunoprecipitation, computational modeling, BAP1 siRNA knockdown, mutagenesis of BAP1 interaction domain, patient mesothelioma biopsy IHC Proceedings of the National Academy of Sciences of the United States of America High 36656861
2017 PER2 (period circadian clock 2) interacts with HIF-1α and functions as an effector molecule facilitating recruitment of HIF-1α to hypoxia response elements (HREs), including the VEGF promoter HRE. PER2-mediated HIF-1 activation requires HIF-1α N803 to be unhydroxylated (by hypoxia, N803A mutation, or FIH inhibitor deferoxamine), though PER2-HIF-1α interaction itself is independent of N803 hydroxylation status. Co-immunoprecipitation, ChIP, luciferase HRE reporter assay, point mutation (N803A), pharmacological FIH inhibition (deferoxamine), PER2 overexpression The FEBS journal Medium 28963769
2019 HIF1A and NFAT5 coordinate high-salt (Na+)-boosted antibacterial defense in macrophages: HIF1A-dependent increased autophagy and NFAT5-dependent targeting of intracellular E. coli to acidic autolysosomal compartments are both required. The antibacterial activity was not dependent on NOS2 or phagocyte oxidase. Conditional KO (LysM-Cre Hif1a and NFAT5 deletion), bacterial colony forming unit assays, autophagic flux assays, lysosomal acidification assays Autophagy Medium 30982460
2021 HIF-1α activates non-canonical target genes in oligodendrocyte progenitor cells (OPCs) through physical interaction with the OPC-specific transcription factor OLIG2; non-canonical targets Ascl2 and Dlx3 suppress Sox10 and block oligodendrocyte differentiation. MEK/ERK inhibition restores Sox10 expression and oligodendrocyte generation without affecting canonical HIF-1α activity. Chronic HIF-1α accumulation model in PSC-derived OPCs, ChIP-seq, gene expression profiling, chemical MEK/ERK inhibitor screen, human oligocortical spheroid model Cell stem cell Medium 33091368
2021 Cardiac fibroblast-specific deletion of Hif-1a leads to increased mitochondrial ROS after myocardial infarction, resulting in ~50% increased cardiac fibroblast proliferation and excessive scarring. The mitochondrial-targeted antioxidant MitoTEMPO rescues the mutant phenotype, indicating HIF-1α acts as a brake against excessive post-ischemic fibroblast activation through regulation of mitochondrial ROS. CF-specific Cre-lox Hif-1a deletion, scRNA-seq, 3D engineered cardiac microtissues, MitoParaquat treatment, MitoTEMPO rescue, ROS measurement Cell stem cell High 34762860
2012 HIF-1α directly binds to functional hypoxia response elements (HREs) in the S100A8 and S100A9 promoters (confirmed by ChIP) and activates their transcription in prostate cancer cells, as demonstrated by promoter luciferase reporter constructs. ChIP, luciferase promoter reporter assay, HIF-1α overexpression, siRNA knockdown, hypoxia treatment International journal of cancer Medium 22505354
2012 HIF1A binds to HRE elements in the WASF3 (WAVE3) gene promoter under hypoxic conditions (confirmed by ChIP), activating WASF3 transcription and promoting cell motility and invasion; WASF3 knockdown abolishes the hypoxic invasion response. ChIP, luciferase reporter assay, WASF3 siRNA knockdown, scratch wound motility assay, hypoxia treatment International journal of cancer Medium 22581642
2009 Intracellular calcium elevation (via ionomycin) and calmodulin activity are required for hypoxia-induced HIF-1 transcriptional activation, acting upstream of the ERK pathway. ERK pathway inhibition (PD98059) blocks HIF-1 activation by both hypoxia and ionomycin without affecting HIF-1α protein level or DNA binding, indicating calcium/calmodulin→ERK regulates HIF-1 transcriptional activity post-DNA binding. Pharmacological inhibition (ionomycin, BAPTA, calmodulin dominant-negative mutant, PD98059, KN-93), HIF-1 reporter assay, electrophoretic mobility shift assay (EMSA) Annals of the New York Academy of Sciences Low 12485909
2019 STAT1 functions as a transcriptional suppressor of HIF1A: ATG7 deletion in endothelial cells upregulates STAT1 (via an autophagy-independent mechanism involving ZNF148/ZFP148 nuclear translocation), which binds the HIF1A promoter and suppresses HIF1A expression, impairing angiogenesis. HIF1A overexpression rescues the ATG7-deficiency angiogenesis defect. EC-specific Atg7 KO mouse, ChIP (STAT1 on HIF1A promoter), HIF1A overexpression rescue, ZNF148 nuclear fractionation, fludarabine STAT1 inhibition Autophagy Medium 36300763
2024 CARM1 is physically associated with and directly interacts with HIF1A; CARM1 is recruited by HIF1A and occupies promoters of CDK4, Cyclin D1, β-Catenin, HIF1A, MALAT1, and SIX1, modulating proliferation and invasion in triple-negative breast cancer. Co-immunoprecipitation, ChIP-seq (genome-wide CARM1 occupancy), siRNA knockdown, overexpression functional assays Protein & cell Medium 38476024
2009 HIF-1α loss from skeletal muscle (conditional KO) increases oxidative capacity and constitutively activates AMP-activated protein kinase (AMPK), decreases expression of pyruvate dehydrogenase kinase I (a HIF-1α target), and increases capillary-to-fiber ratio, demonstrating HIF-1α normally suppresses mitochondrial biogenesis and oxidative metabolism in skeletal muscle. Skeletal muscle-specific Hif-1α KO mice, respiratory exchange ratio, capillary density quantification, oxidative enzyme activity, AMPK activation assay Advances in experimental medicine and biology Medium 18269201
2020 In bovine granulosa cells, HIF1 transcriptionally regulates steroidogenesis genes (STAR, HSD3B, CYP19A1) and proliferation genes (CCND2, PCNA); CYP19A1 (aromatase) is a direct downstream target of HIF1, as demonstrated by ChIP showing HIF1A binding to its promoter. Echinomycin inhibition, siRNA knockdown, ChIP, radioimmunoassay (estradiol), RT-qPCR Scientific reports Medium 32127571
2009 HIF-1 activates transcription of pyruvate dehydrogenase kinase 1 (PDK1), which shunts pyruvate away from mitochondria, and BNIP3, which triggers selective mitochondrial autophagy, thereby coordinating a shift from oxidative phosphorylation to glycolysis under hypoxia. Transcriptional target gene analysis, reporter assays, genetic deletion models (synthesized in review of primary experiments) Current opinion in genetics & development Medium 19942427

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Targeting HIF-1 for cancer therapy. Nature reviews. Cancer 5451 13130303
2000 HIF-1: mediator of physiological and pathophysiological responses to hypoxia. Journal of applied physiology (Bethesda, Md. : 1985) 1438 10749844
2006 Hypoxia-inducible factor-1 (HIF-1). Molecular pharmacology 1320 16887934
2009 HIF-1: upstream and downstream of cancer metabolism. Current opinion in genetics & development 1082 19942427
2013 HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations. The Journal of clinical investigation 1073 23999440
2001 HIF-1 and mechanisms of hypoxia sensing. Current opinion in cell biology 1022 11248550
2002 HIF-1 and tumor progression: pathophysiology and therapeutics. Trends in molecular medicine 829 11927290
2007 Hypoxia-inducible factor 1 (HIF-1) pathway. Science's STKE : signal transduction knowledge environment 733 17925579
2015 HIF-1 at the crossroads of hypoxia, inflammation, and cancer. International journal of cancer 457 25784597
2005 HIF-1alpha induces genetic instability by transcriptionally downregulating MutSalpha expression. Molecular cell 289 15780936
2008 HIF-1 regulation: not so easy come, easy go. Trends in biochemical sciences 279 18809331
2018 Role of HIF-1 in Cancer Progression: Novel Insights. A Review. Current molecular medicine 252 30411685
2007 HIF-1 and HIF-2: working alone or together in hypoxia? The Journal of clinical investigation 232 17404612
2000 HIF-1: using two hands to flip the angiogenic switch. Cancer metastasis reviews 208 11191064
2004 Intratumoral hypoxia, radiation resistance, and HIF-1. Cancer cell 199 15144945
2004 HIF-1: an oxygen and metal responsive transcription factor. Cancer biology & therapy 191 14726713
2009 Relationships between cycling hypoxia, HIF-1, angiogenesis and oxidative stress. Radiation research 189 19929412
2021 Hif-1a suppresses ROS-induced proliferation of cardiac fibroblasts following myocardial infarction. Cell stem cell 185 34762860
2010 HIF-1alpha dysfunction in diabetes. Cell cycle (Georgetown, Tex.) 167 20016290
2001 Jab1 interacts directly with HIF-1alpha and regulates its stability. The Journal of biological chemistry 161 11707426
2001 HIF-1 expression in healing wounds: HIF-1alpha induction in primary inflammatory cells by TNF-alpha. American journal of physiology. Cell physiology 160 11698256
2004 HIF-1 and p53: communication of transcription factors under hypoxia. Journal of cellular and molecular medicine 150 15601571
2008 Distinct size distribution of endogeneous siRNAs in maize: Evidence from deep sequencing in the mop1-1 mutant. Proceedings of the National Academy of Sciences of the United States of America 149 18815367
2010 Role of HIF-1alpha in skeletal development. Annals of the New York Academy of Sciences 148 20392254
2007 RACK1 vs. HSP90: competition for HIF-1 alpha degradation vs. stabilization. Cell cycle (Georgetown, Tex.) 140 17361105
2004 HIF-1 and hypoxic response: the plot thickens. Current opinion in genetics & development 128 15108809
2004 New anticancer strategies targeting HIF-1. Biochemical pharmacology 128 15313402
2009 HIF-1: a key mediator in hypoxia. Acta physiologica Hungarica 125 19264039
2004 HIF-1: master and commander of the hypoxic world. A pharmacological approach to its regulation by siRNAs. Biochemical pharmacology 119 15313390
2003 HIF-1 in cell cycle regulation, apoptosis, and tumor progression. Antioxidants & redox signaling 101 13678535
2017 Role of AHR and HIF-1α in Glioblastoma Metabolism. Trends in endocrinology and metabolism: TEM 100 28318896
2014 HIF-1 signaling in drug resistance to chemotherapy. Current medicinal chemistry 96 24735366
2022 ALKBH5-mediated m6A modification of circCCDC134 facilitates cervical cancer metastasis by enhancing HIF1A transcription. Journal of experimental & clinical cancer research : CR 94 36028854
2007 HIF-1 regulates hypoxia- and insulin-induced expression of apelin in adipocytes. American journal of physiology. Endocrinology and metabolism 91 17878221
2016 Hyperthermia induced HIF-1a expression of lung cancer through AKT and ERK signaling pathways. Journal of experimental & clinical cancer research : CR 85 27456341
2005 Hypoxia and HIF-1 alpha in chondrogenesis. Seminars in cell & developmental biology 84 16144691
1995 Schizosaccharomyces pombe Mop1-Mcs2 is related to mammalian CAK. The EMBO journal 78 8557036
2016 Hypoxia and HIF-1 activation in bacterial infections. Microbes and infection 76 27903434
2021 Flavonoids Targeting HIF-1: Implications on Cancer Metabolism. Cancers 75 33401572
2019 HIF-1 transcription activity: HIF1A driven response in normoxia and in hypoxia. BMC medical genetics 73 30808328
2014 Hypoxia sustains glioblastoma radioresistance through ERKs/DNA-PKcs/HIF-1α functional interplay. International journal of oncology 73 24676782
2017 A circadian clock gene, PER2, activates HIF-1 as an effector molecule for recruitment of HIF-1α to promoter regions of its downstream genes. The FEBS journal 70 28963769
2012 The growing complexity of HIF-1α's role in tumorigenesis: DNA repair and beyond. Oncogene 67 23160373
2017 HIF1A up-regulates the ADORA2B receptor on alternatively activated macrophages and contributes to pulmonary fibrosis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 65 28701304
2012 Hypoxia and HIF-1 increase S100A8 and S100A9 expression in prostate cancer. International journal of cancer 62 22505354
2019 HIF-transcribed p53 chaperones HIF-1α. Nucleic acids research 59 31538203
2010 HIF-1alpha and cancer therapy. Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer 59 20033376
2022 PRMT3 drives glioblastoma progression by enhancing HIF1A and glycolytic metabolism. Cell death & disease 58 36351894
2022 Ferroptosis-related gene NOX4, CHAC1 and HIF1A are valid biomarkers for stomach adenocarcinoma. Journal of cellular and molecular medicine 57 35023280
2008 Feminized tassels of maize mop1 and ts1 mutants exhibit altered levels of miR156 and specific SBP-box genes. Planta 57 18800226
2009 Mutation analysis of hypoxia-inducible factors HIF1A and HIF2A in renal cell carcinoma. Anticancer research 54 20032376
2008 HIF-1 and ventilatory acclimatization to chronic hypoxia. Respiratory physiology & neurobiology 53 18708172
2018 The long noncoding RNA HIF1A-AS2 facilitates cisplatin resistance in bladder cancer. Journal of cellular biochemistry 51 30216500
2019 HIF1A and NFAT5 coordinate Na+-boosted antibacterial defense via enhanced autophagy and autolysosomal targeting. Autophagy 50 30982460
2011 HIF-1 as a target for cancer chemotherapy, chemosensitization and chemoprevention. Current molecular pharmacology 50 20958262
2005 The mop1 (mediator of paramutation1) mutant progressively reactivates one of the two genes encoded by the MuDR transposon in maize. Genetics 49 16219782
2022 HNRNPC downregulation inhibits IL-6/STAT3-mediated HCC metastasis by decreasing HIF1A expression. Cancer science 48 35848884
2020 HIF1 driven transcriptional activity regulates steroidogenesis and proliferation of bovine granulosa cells. Scientific reports 48 32127571
2002 ERK and calcium in activation of HIF-1. Annals of the New York Academy of Sciences 47 12485909
2020 Non-canonical Targets of HIF1a Impair Oligodendrocyte Progenitor Cell Function. Cell stem cell 46 33091368
2007 The role of HIF-1 in hypoxic response in the skeletal muscle. Advances in experimental medicine and biology 46 18269201
2022 Cholesterol and HIF-1α: Dangerous Liaisons in Atherosclerosis. Frontiers in immunology 45 35386720
2021 HIF‑1α in cerebral ischemia (Review). Molecular medicine reports 45 34878158
2019 Modeling the regulation of p53 activation by HIF-1 upon hypoxia. FEBS letters 45 31282018
2017 KDM4A regulates HIF-1 levels through H3K9me3. Scientific reports 45 28894274
2006 Hypoxia and HIF-1alpha in chondrogenesis. Annals of the New York Academy of Sciences 44 16831906
2017 Regulation of glycolysis in brown adipocytes by HIF-1α. Scientific reports 42 28642579
2013 AGR2 expression is regulated by HIF-1 and contributes to growth and angiogenesis of glioblastoma. Cell biochemistry and biophysics 42 23712868
2023 USP51 facilitates colorectal cancer stemness and chemoresistance by forming a positive feed-forward loop with HIF1A. Cell death and differentiation 41 37816999
2020 HIF-1a regulates hypoxia-induced autophagy via translocation of ANKRD37 in colon cancer. Experimental cell research 41 32679233
2017 Circulating exosomes and exosomal lncRNA HIF1A-AS1 in atherosclerosis. International journal of clinical and experimental pathology 39 31966690
2022 HIF1, HSF1, and NRF2: Oxidant-Responsive Trio Raising Cellular Defenses and Engaging Immune System. Chemical research in toxicology 38 35948068
2017 HIF1A gene polymorphisms and human diseases: Graphical review of 97 association studies. Genes, chromosomes & cancer 36 28165644
2016 HIF-1--a big chapter in the cancer tale. Experimental oncology 36 27031712
2019 EGLN2 DNA methylation and expression interact with HIF1A to affect survival of early-stage NSCLC. Epigenetics 35 30665327
2019 Improved Motor Nerve Regeneration by SIRT1/Hif1a-Mediated Autophagy. Cells 35 31671642
2018 The p38α Stress Kinase Suppresses Aneuploidy Tolerance by Inhibiting Hif-1α. Cell reports 34 30332653
2020 Independence of HIF1a and androgen signaling pathways in prostate cancer. BMC cancer 33 32450824
2019 Transferrin receptor-involved HIF-1 signaling pathway in cervical cancer. Cancer gene therapy 33 30651591
2023 HIF-1 signaling: an emerging mechanism for mitochondrial dynamics. Journal of physiology and biochemistry 31 37178248
2019 Non-canonical HIF-1 stabilization contributes to intestinal tumorigenesis. Oncogene 31 31043706
2012 HIF1A induces expression of the WASF3 metastasis-associated gene under hypoxic conditions. International journal of cancer 31 22581642
2018 Adverse effects of Hif1a mutation and maternal diabetes on the offspring heart. Cardiovascular diabetology 29 29753320
2025 Research progress of HIF-1a on immunotherapy outcomes in immune vascular microenvironment. Frontiers in immunology 28 39981236
2022 Ablation of endothelial Atg7 inhibits ischemia-induced angiogenesis by upregulating Stat1 that suppresses Hif1a expression. Autophagy 28 36300763
2024 Citrullination modulation stabilizes HIF-1α to promote tumour progression. Nature communications 26 39227578
2022 Intermittent hypoxia enhances the expression of hypoxia inducible factor HIF1A through histone demethylation. The Journal of biological chemistry 26 36174675
2018 PAFAH1B2 is a HIF1a target gene and promotes metastasis in pancreatic cancer. Biochemical and biophysical research communications 26 29758199
2017 HIF has Biff - Crosstalk between HIF1a and the family of bHLH/PAS proteins. Experimental cell research 26 28366537
2023 BAP1 is a novel regulator of HIF-1α. Proceedings of the National Academy of Sciences of the United States of America 25 36656861
2009 TNFalpha induces HIF-1alpha expression through activation of IKKbeta. Biochemical and biophysical research communications 25 19766100
2023 FSHR-mTOR-HIF1 signaling alleviates mouse follicles from AMPK-induced atresia. Cell reports 24 37733588
2020 Inhibition of HIF1A-AS1 promoted starvation-induced hepatocellular carcinoma cell apoptosis by reducing HIF-1α/mTOR-mediated autophagy. World journal of surgical oncology 24 32473641
2006 Leukocyte's Hif-1 expression and training-induced erythropoietic response in swimmers. Medicine and science in sports and exercise 24 16888453
2015 Expression and significance of FOXP1, HIF-1a and VEGF in renal clear cell carcinoma. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 23 25778315
2013 HIF-1α in heart: protective mechanisms. American journal of physiology. Heart and circulatory physiology 23 23873797
2018 TGF-b1 or hypoxia enhance glucose metabolism and lactate production via HIF1A signaling in tendon cells. Connective tissue research 22 29447016
2024 Metabolic Roles of HIF1, c-Myc, and p53 in Glioma Cells. Metabolites 21 38786726
2021 Integrative Map of HIF1A Regulatory Elements and Variations. Genes 21 34680921
2024 CARM1 drives triple-negative breast cancer progression by coordinating with HIF1A. Protein & cell 20 38476024

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