Affinage

HIF1A

Hypoxia-inducible factor 1-alpha · UniProt Q16665

Round 2 corrected
Length
826 aa
Mass
92.7 kDa
Annotated
2026-04-28
130 papers in source corpus 47 papers cited in narrative 47 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HIF-1α is the oxygen-regulated α subunit of the HIF-1 heterodimeric transcription factor that serves as a master regulator of cellular adaptation to hypoxia, controlling transcriptional programs for glycolysis, angiogenesis, epithelial–mesenchymal transition, immune cell differentiation, and mitochondrial remodeling (PMID:1448077, PMID:8089148, PMID:8756616, PMID:17418790, PMID:21871655). Under normoxia, prolyl hydroxylase PHD2 hydroxylates Pro402/Pro564 within the oxygen-dependent degradation domain, enabling pVHL-mediated ubiquitination and proteasomal destruction, while FIH-1 hydroxylates Asn803 in the C-terminal transactivation domain to block p300/CBP coactivator recruitment; both hydroxylation events require Fe²⁺ and O₂ as cofactors and are suppressed under hypoxia, permitting HIF-1α stabilization, nuclear translocation, heterodimerization with ARNT (HIF-1β), and transcriptional activation at hypoxia-response elements (PMID:11292861, PMID:11292862, PMID:12912907, PMID:12080085, PMID:7539918). HIF-1α stability is further tuned by O₂-independent mechanisms including RACK1-mediated Elongin-C/B ubiquitination competing with HSP90 chaperoning, PADI4 citrullination at R698 that blocks VHL binding, and deubiquitination by BAP1 and USP51 (PMID:17361105, PMID:39227578, PMID:36656861, PMID:37816999). Beyond canonical hypoxia targets, HIF-1α cooperates with lineage-specific factors such as OLIG2 in oligodendrocyte progenitors and RORγt in T cells to activate context-dependent gene programs, and its transcription is itself regulated by KDM4A-mediated H3K9me3 demethylation at the HIF1A locus and STAT1-mediated repression (PMID:33091368, PMID:21871655, PMID:28894274, PMID:36300763).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1992 High

    Identification of a hypoxia-inducible nuclear factor (HIF-1) that binds the erythropoietin enhancer established the existence of a dedicated transcriptional oxygen-sensing pathway.

    Evidence DNase I footprinting and EMSA with cycloheximide block in Hep3B cells

    PMID:1448077

    Open questions at the time
    • Identity of HIF-1 subunits unknown
    • Mechanism of O₂-dependent induction undefined
    • Generality beyond EPO gene not tested
  2. 1995 High

    Purification and cloning of HIF-1 as a bHLH-PAS heterodimer of HIF-1α and ARNT (HIF-1β) resolved its molecular architecture and showed both subunits contact DNA, while parallel work established HIF-1 as a general hypoxia mediator across cell types activating glycolytic and VEGF genes.

    Evidence Protein purification, UV cross-linking, cloning, EMSA/reporter assays in multiple cell lines and HRE mutagenesis

    PMID:7539918 PMID:7836384 PMID:8089148 PMID:8387214 PMID:8756616

    Open questions at the time
    • Mechanism of O₂-dependent protein instability unknown
    • No post-translational modification identified
    • Coactivator recruitment mechanism undefined
  3. 1998 High

    Mapping the oxygen-dependent degradation (ODD) domain showed that a ~200 aa central region is both necessary and sufficient for O₂-regulated proteasomal degradation, narrowing the search for the oxygen-sensing modification.

    Evidence Systematic domain deletion and fusion-protein stability assays under normoxia/hypoxia

    PMID:9653127

    Open questions at the time
    • Identity of the E3 ligase targeting the ODD unknown
    • Nature of the O₂-dependent modification undefined
  4. 1999 High

    Discovery that pVHL targets HIF-1α for O₂-dependent proteolysis provided the E3 ligase link, while HSP90 was identified as a normoxic chaperone of the bHLH-PAS domain required for HIF-1 competence.

    Evidence VHL re-expression rescue in VHL-null cells, co-IP, iron chelation; EGFP-HIF-1α co-IP and geldanamycin inhibition

    PMID:10353251 PMID:10544245

    Open questions at the time
    • Molecular basis of O₂-dependent VHL–HIF-1α binding unknown
    • Nature of the iron-dependent signal unresolved
  5. 2001 High

    The oxygen-sensing mechanism was resolved: prolyl hydroxylases (PHD/HPH) hydroxylate Pro564 (and Pro402) using O₂ and Fe²⁺ as cofactors, creating the pVHL-binding epitope; simultaneously FIH-1 was identified as a VHL-interacting protein that represses HIF-1α transactivation.

    Evidence Peptide binding assays, site-directed mutagenesis, mass spectrometry, in vitro hydroxylation reconstitution, RNAi in Drosophila, yeast two-hybrid and reporter assays for FIH-1

    PMID:10878807 PMID:11292861 PMID:11292862 PMID:11598268 PMID:11641274 PMID:11707426

    Open questions at the time
    • Whether FIH-1 is also a hydroxylase not yet shown
    • Relative contributions of PHD1/2/3 unresolved
    • No structural model of hydroxylated HIF–VHL complex
  6. 2002 High

    FIH-1 was shown to be an asparaginyl hydroxylase modifying Asn803, which blocks p300/CBP recruitment; full HIF-1 activation requires abrogation of both prolyl and asparaginyl hydroxylation, establishing a dual oxygen-sensing checkpoint; mTOR was identified as an O₂-independent positive regulator acting through the ODD domain.

    Evidence In vitro hydroxylation with MS, Asn→Ala mutagenesis, p300 interaction assays; rapamycin inhibition with rapamycin-resistant mTOR rescue and ODD domain mapping

    PMID:11823643 PMID:12080085 PMID:12242281

    Open questions at the time
    • Structural basis of Asn-OH blocking p300 unknown
    • mTOR mechanism on ODD not molecularly defined
    • In vivo validation of dual checkpoint limited
  7. 2003 High

    PHD2 was identified as the critical prolyl hydroxylase setting normoxic HIF-1α levels, and HIF-1α was shown to specifically govern glycolytic gene expression (distinct from HIF-2α), establishing non-redundant target gene programs.

    Evidence Systematic siRNA knockdown of PHD1/2/3 in multiple human cell lines; DNA microarray comparison of HIF-1α−/− cells with regulated HIF-1α or HIF-2α re-expression

    PMID:12912907 PMID:14645546

    Open questions at the time
    • Whether PHD2 dominance holds in all tissues unknown
    • Chromatin-level basis of target gene selectivity unresolved
  8. 2005 High

    Succinate accumulation from SDH deficiency was shown to inhibit PHDs and stabilize HIF-1α, linking TCA cycle mutations to pseudo-hypoxic oncogenic signaling.

    Evidence SDH knockdown/inhibition with direct PHD activity assays and HIF-1α stability measurements

    PMID:15652751

    Open questions at the time
    • Whether fumarate acts similarly not yet addressed
    • Quantitative kinetic parameters of metabolite-PHD inhibition undefined
  9. 2007 High

    RACK1 was identified as a VHL/PHD-independent degradation pathway for HIF-1α, competing with HSP90 for the PAS-A domain and recruiting Elongin-C/B; separately, HIF-1 was shown to switch mitochondrial COX subunit composition (COX4-1→COX4-2) via LON protease induction, optimizing respiration at low O₂.

    Evidence RACK1 co-IP, domain competition, ubiquitination assay, siRNA; COX subunit ChIP, reporter, siRNA, metabolic flux and in vivo mouse model

    PMID:17361105 PMID:17418790

    Open questions at the time
    • Physiological contexts where RACK1 pathway dominates unclear
    • Structural basis of RACK1–HSP90 competition undefined
  10. 2008 High

    HIF-1α was shown to directly transactivate TWIST to drive EMT and metastasis, and to respond to non-hypoxic stimuli (mechanical wounding via PI3K), broadening the functional scope beyond classical hypoxia targets.

    Evidence ChIP at TWIST promoter, siRNA rescue of EMT; PI3K inhibition and scratch-wound assay with laminin-332 reporter

    PMID:18297062 PMID:18713836

    Open questions at the time
    • Whether TWIST is a direct or cooperative HIF-1α target in all cancer contexts unknown
    • PI3K-HIF-1α stabilization mechanism not molecularly defined
  11. 2011 High

    Two major coactivator mechanisms were defined: PKM2 (itself hydroxylated by PHD3) acts as a HIF-1α coactivator enhancing p300 recruitment in a metabolic positive-feedback loop; HIF-1α drives TH17/Treg balance by activating RORγt while targeting Foxp3 for degradation, establishing HIF-1α as a lymphocyte fate regulator.

    Evidence PKM2 co-IP, ChIP, MS of hydroxylation, metabolic assays; T-cell-specific HIF-1α conditional KO mice, co-IP with Foxp3, EAE model

    PMID:21620138 PMID:21871655

    Open questions at the time
    • Whether PKM2-HIF-1α axis operates in non-cancer tissues unclear
    • Mechanism of HIF-1α-mediated Foxp3 proteasomal targeting not fully defined
  12. 2016 High

    TIP60 (KAT5) was identified as a conserved HIF-1α coactivator required for chromatin modification and RNA Pol II activation at HREs but dispensable for HIF-1α DNA binding, separating chromatin remodeling from target-site recognition.

    Evidence Co-IP, ChIP-seq, genetic knockdown in Drosophila and human cells, RNA Pol II ChIP

    PMID:27320910

    Open questions at the time
    • Whether TIP60 is required at all HIF-1 target genes or a subset unknown
    • Relationship between TIP60 and p300 coactivator functions not delineated
  13. 2020 High

    HIF-1α was shown to activate non-canonical gene programs through interaction with lineage-specific transcription factors (OLIG2 in OPCs), suppressing Sox10 and blocking oligodendrocyte differentiation; MEK/ERK inhibition selectively reversed this non-canonical activity.

    Evidence ChIP-seq in OPCs, OLIG2 co-IP, gain-of-function, MEK inhibitor rescue, human oligocortical spheroids

    PMID:33091368

    Open questions at the time
    • Whether other lineage-specific TF partners redirect HIF-1α in additional cell types is unexplored
    • Structural basis of HIF-1α–OLIG2 interaction unknown
  14. 2022 High

    O₂-independent regulatory inputs to HIF-1α were expanded: PADI4 citrullinates R698 to block VHL binding, KDM4A demethylates H3K9me3 at the HIF1A locus to control its transcription (with distinct dynamics under intermittent vs. chronic hypoxia), and STAT1 acts as a transcriptional repressor of HIF1A downstream of ATG7/ZNF148.

    Evidence In vitro citrullination with MS, VHL binding/ubiquitination assays; H3K9me3 ChIP at HIF1A locus under intermittent/chronic hypoxia; EC-specific Atg7 KO with STAT1 ChIP at HIF1A promoter and rescue experiments

    PMID:28894274 PMID:36174675 PMID:36300763 PMID:39227578

    Open questions at the time
    • Physiological triggers of PADI4-mediated citrullination of HIF-1α in vivo unknown
    • How intermittent vs. chronic hypoxia differentially controls KDM4 activity mechanistically unclear
  15. 2023 High

    Two deubiquitinases were identified as direct HIF-1α stabilizers: BAP1 binds HIF-1α through defined C-terminal residues and its loss reduces nuclear HIF-1α in mesothelioma; USP51 forms a complex with VHL/Elongin-C to deubiquitinate HIF-1α, with SENP1-mediated deSUMOylation of Elongin-C promoting this interaction, creating a transcriptional positive-feedback loop.

    Evidence Co-IP, mutagenesis of BAP1 binding interface, deubiquitination assays, clinical mesothelioma validation; USP51–VHL–ELOC complex co-IP, ChIP of HIF-1α at USP51 promoter, ELOC K32 SUMOylation mutagenesis

    PMID:36656861 PMID:37816999

    Open questions at the time
    • Relative quantitative contributions of BAP1 vs. USP51 to HIF-1α pool in different tissues unknown
    • Whether BAP1 deubiquitination opposes VHL-specific ubiquitin chains or broader ubiquitin conjugates not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how lineage-specific transcription factor partnerships (beyond OLIG2 and RORγt) redirect HIF-1α target gene selection genome-wide; the structural basis of the RACK1–HSP90 competition at the PAS-A domain; quantitative integration of the multiple PHD-independent stabilization inputs (PADI4, BAP1, USP51, RACK1, mTOR) in physiological contexts; and whether intermittent versus chronic hypoxia engage fundamentally different HIF-1α regulatory circuits in vivo.
  • Genome-wide chromatin accessibility basis for context-dependent HIF-1α target selection unknown
  • No integrated quantitative model of competing stabilization/degradation signals
  • In vivo validation of many O₂-independent regulatory mechanisms limited to single tissue models

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 10 GO:0003677 DNA binding 6
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 2
Pathway
R-HSA-74160 Gene expression (Transcription) 8 R-HSA-8953897 Cellular responses to stimuli 7 R-HSA-392499 Metabolism of proteins 6 R-HSA-1430728 Metabolism 4 R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-168256 Immune System 2
Partners
ARNTBAP1EGLN1EP300HIF1ANKAT5PKMVHL
Complex memberships
HIF-1 (HIF-1α/ARNT heterodimer)VHL-Elongin-C/B E3 ligase complex

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 A nuclear factor (HIF-1) is induced by hypoxia via de novo protein synthesis and binds to a site in the human erythropoietin gene enhancer required for transcriptional activation, establishing HIF-1 as a hypoxia-responsive transcriptional activator. DNase I footprinting, EMSA, reporter gene transfection, cycloheximide inhibition Molecular and cellular biology High 1448077
1993 HIF-1 DNA-binding activity is induced by hypoxia in a wide variety of mammalian cell types (not only EPO-producing cells), establishing HIF-1 as a general mediator of transcriptional responses to hypoxia. EMSA, reporter gene transfection, mutagenesis across multiple cell lines Proceedings of the National Academy of Sciences of the United States of America High 8387214
1994 HIF-1 directly binds to HRE sequences in the promoters of glycolytic enzyme genes (aldolase A, PGK1, enolase 1, LDHA, PFKL) and activates their transcription under hypoxia, linking HIF-1 to metabolic reprogramming. EMSA with affinity-purified HIF-1, reporter gene transfection with HRE sequences, RNA induction assays The Journal of biological chemistry High 8089148
1995 HIF-1 is a heterodimer of two bHLH-PAS proteins: HIF-1α (most closely related to Drosophila Sim) and HIF-1β (ARNT). Both subunits are induced at 1% O₂ and decay upon reoxygenation. Protein purification, biochemical characterization, molecular cloning, RNA/protein level measurements under hypoxia Proceedings of the National Academy of Sciences of the United States of America High 7539918
1995 HIF-1 purified as a heterodimer (~120 kDa HIF-1α and 91–94 kDa HIF-1β subunits); both subunits contact DNA directly; HIF-1 binds specifically to the wild-type EPO enhancer HIF-1 binding site. Affinity chromatography purification, UV cross-linking, glycerol gradient sedimentation, EMSA The Journal of biological chemistry High 7836384
1996 HIF-1 directly activates VEGF transcription by binding to a hypoxia-response element (HRE) in the VEGF 5'-flanking region; dominant-negative HIF-1α abolishes hypoxic VEGF induction; HIF-1β (ARNT)-null cells fail to induce VEGF mRNA. Reporter gene assays, HRE mutagenesis, dominant-negative cotransfection, ARNT-null cell lines Molecular and cellular biology High 8756616
1998 HIF-1α contains an oxygen-dependent degradation (ODD) domain (~200 aa in the central region) that controls its ubiquitin-proteasome degradation; deletion of the entire ODD yields a stable, functional HIF-1α under normoxia; ODD alone confers O₂-dependent instability when fused to a stable protein. Domain deletion mutagenesis, fusion-protein stability assays, heterodimerization and transactivation assays Proceedings of the National Academy of Sciences of the United States of America High 9653127
1999 pVHL targets HIF-α subunits for oxygen-dependent proteolysis: VHL-defective cells constitutively stabilize HIF-α; re-expression of pVHL restores O₂-dependent instability; pVHL and HIF-α co-immunoprecipitate and the interaction is iron-dependent. VHL re-expression in VHL-null cells, co-immunoprecipitation, iron chelation experiments Nature High 10353251
1999 Hsp90 interacts with the bHLH-PAS domain of HIF-1α under normoxia but not hypoxia; Hsp90 is not co-translocated to the nucleus with HIF-1α; Hsp90 activity is required for HIF-1 activation (inhibited by geldanamycin). EGFP-HIF-1α co-immunoprecipitation in COS-7 cells, domain mapping, geldanamycin pharmacological inhibition FEBS letters Medium 10544245
2000 pVHL, through its β-domain, directly binds HIF-α and targets it for ubiquitination in an α-domain-dependent manner, providing the first evidence that pVHL functions analogously to an F-box protein recruiting substrates to the ubiquitination machinery. Direct binding assays, ubiquitination assays, domain mutagenesis Nature cell biology High 10878807
2001 HIF-1α is targeted for VHL-mediated ubiquitylation through O₂-regulated hydroxylation of proline residue P564 by a HIF-α prolyl-hydroxylase (HIF-PH/PHD); the reaction requires dioxygen and Fe²⁺ as cofactors, identifying PHD as the direct cellular oxygen sensor. Peptide binding assays, site-directed mutagenesis (P564), mass spectrometry, in vitro hydroxylation with Fe²⁺/O₂ Science High 11292861
2001 pVHL binds HIF-1α-derived peptide only when a conserved proline is hydroxylated; proline hydroxylation requires molecular O₂ and Fe²⁺, placing this modification as the key oxygen-sensing step in HIF-1α degradation. Peptide binding assay, site-directed mutagenesis, Fe²⁺/O₂ dependency experiments Science High 11292862
2001 FIH-1 binds both HIF-1α and pVHL; FIH-1 inhibits HIF-1α transactivation function; VHL also acts as a transcriptional corepressor by recruiting histone deacetylases to inhibit HIF-1α transactivation independently of protein degradation. Yeast two-hybrid, co-immunoprecipitation, reporter assays, HDAC recruitment assays Genes & development High 11641274
2001 Jab1 (COP9 signalosome subunit 5) directly interacts with HIF-1α, enhances HIF-1 transcriptional activity, increases HIF-1α protein stability, and interferes with p53–HIF-1α binding in a Jab1-dependent manner. Yeast two-hybrid, GST pull-down, co-immunoprecipitation, reporter assays The Journal of biological chemistry Medium 11707426
2001 A conserved family of HIF prolyl-hydroxylase (HPH/PHD) enzymes hydroxylates the ODD proline of HIF-1α; forced HIF-1α expression under normoxia is attenuated by HPH co-expression; RNAi knockdown of HPH in Drosophila cells elevates a hypoxia-inducible gene under normoxia. Sequence homology, co-expression normoxic stabilization assay, Drosophila cell RNAi Science High 11598268
2002 FIH-1 is an asparaginyl hydroxylase (Fe[II]-dependent, O₂-dependent dioxygenase) that hydroxylates a conserved asparagine in the C-terminal transactivation domain (CAD) of HIF-1α, blocking p300/CBP coactivator recruitment under normoxia. In vitro hydroxylation assay, mass spectrometry, Asn→Ala mutagenesis, p300 interaction assays Genes & development High 12080085
2002 Hypoxic induction of the HIF CAD requires abrogation of asparagine hydroxylation, which in normoxia prevents p300 coactivator interaction; Asn→Ala substitution yields constitutive p300 interaction and strong transcriptional activity; full HIF induction requires abrogation of both Pro and Asn hydroxylation. Dioxygenase inhibitors, Asn mutagenesis, p300 interaction assays, transcriptional reporter assays Science High 11823643
2002 mTOR signaling promotes HIF-1α stabilization and HIF-1 transactivation; rapamycin inhibits hypoxia- and CoCl₂-induced HIF-1α accumulation; the ODD domain is the critical target of the rapamycin-sensitive mTOR pathway for HIF-1α stabilization. Rapamycin pharmacological inhibition, wild-type/rapamycin-resistant mTOR transfection, GAL4-HIF-1α domain mapping, reporter assays Molecular and cellular biology High 12242281
2002 Calcium/calmodulin signaling and ERK pathway activation contribute to HIF-1 transcriptional activity under hypoxia; ionomycin additively activates HIF-1 without affecting HIF-1α protein level; calmodulin dominant-negative or BAPTA (Ca²⁺ chelator) inhibits hypoxia-induced HIF-1 activation; PD98059 (MEK inhibitor) blocks HIF-1 activation, placing Ca²⁺/calmodulin upstream of ERK. Pharmacological inhibitors, dominant-negative calmodulin, intracellular Ca²⁺ chelation, reporter assays Annals of the New York Academy of Sciences Medium 12485909
2003 PHD2 is the key oxygen sensor that sets low steady-state HIF-1α levels in normoxia; siRNA silencing of PHD2 alone is sufficient to stabilize and activate HIF-1α in all human cells tested under normoxia; silencing PHD1 or PHD3 has no effect on HIF-1α stability. siRNA knockdown of PHD1, PHD2, PHD3 individually in multiple human cell lines, HIF-1α stability and transcriptional activity assays The EMBO journal High 12912907
2003 HIF-1α (not HIF-2α) is specifically required for glycolytic gene expression; HIF-2α can regulate a subset of broadly expressed hypoxia-inducible genes, demonstrating distinct non-redundant transcriptional programs for the two HIF-α paralogs. DNA microarray analysis of HIF-1α−/− cells, tetracycline-regulated stabilized HIF-1α or HIF-2α expression in HEK293 cells Molecular and cellular biology High 14645546
2005 Succinate accumulation from SDH inhibition inhibits HIF-α prolyl hydroxylases in the cytosol, leading to HIF-1α stabilization and activation, thus linking mitochondrial TCA cycle dysfunction to HIF-1 oncogenic signaling. SDH inhibition/knockdown, prolyl hydroxylase activity assay with succinate, HIF-1α stability assays Cancer cell High 15652751
2005 HIF-1α promotes genetic instability by transcriptionally repressing MSH2 and MSH6 (MutSα mismatch repair complex) through displacing Myc from Sp1 binding sites at their promoters, in a p53-dependent manner. Reporter assays, chromatin immunoprecipitation, siRNA knockdown, co-immunoprecipitation, clinical specimen correlation Molecular cell High 15780936
2007 RACK1 competes with HSP90 for binding to the PAS-A domain of HIF-1α and promotes O₂/PHD/VHL-independent proteasomal degradation of HIF-1α by recruiting Elongin-C/B E3 ubiquitin ligase; RACK1 is required for HSP90 inhibitor-induced HIF-1α degradation. Co-immunoprecipitation, domain mapping, ubiquitination assays, RACK1 siRNA knockdown Cell cycle High 17361105
2007 MgcRacGAP directly binds HIF-1α (verified in vitro and in vivo); MgcRacGAP overexpression inhibits HIF-1α transcriptional activity without affecting HIF-1α protein levels or subcellular localization; inhibition depends on the MgcRacGAP domain that interacts with HIF-1α. Yeast two-hybrid, in vitro pull-down, co-immunoprecipitation in mammalian cells, reporter assays, domain mutagenesis Cellular physiology and biochemistry Medium 17982282
2007 HIF-1 regulates COX4 subunit composition in mammalian cells under hypoxia: HIF-1 activates transcription of COX4-2 and LON (a mitochondrial protease that degrades COX4-1), switching COX subunit composition to optimize respiratory efficiency at low O₂. ChIP, reporter assays, siRNA knockdown, oxygen consumption/ROS/ATP measurements, in vivo mouse model Cell High 17418790
2008 HIF-1 directly binds the HRE in the TWIST proximal promoter to transcriptionally activate TWIST, thereby promoting epithelial-mesenchymal transition (EMT) and cancer metastasis; siRNA knockdown of TWIST reverses HIF-1α-driven EMT. ChIP, reporter assays, siRNA knockdown, EMT/invasion assays, clinical specimen analysis Nature cell biology High 18297062
2008 HIF1 transcription factor is activated by mechanical wounding of keratinocytes (via PI3K pathway, independently of O₂), and directly regulates laminin-332 (laminα3 chain promoter) expression to promote keratinocyte migration and wound re-epithelialization. HIF-1α protein stabilization assays, PI3K inhibition, siRNA knockdown of HIF-1α, reporter assay of laminin α3 promoter, scratch wound assay Journal of cell science Medium 18713836
2009 Acriflavine directly binds HIF-1α and HIF-2α and inhibits HIF-1 dimerization and transcriptional activity; this small molecule prevents tumor growth and vascularization in prostate cancer xenografts. Cell-based reporter screening, direct binding assay, dimerization assay, xenograft tumor models Proceedings of the National Academy of Sciences of the United States of America High 19805192
2009 TNFα enhances HIF-1α protein expression (not mRNA) through IKKβ in breast cancer cells; IKKβ stable overexpression increases HIF-1α protein; IKKβ siRNA depletion or pharmacological inhibition (Bay 11-7082) reduces TNFα-induced HIF-1α; IKKβ-knockout MEFs show reduced VEGF expression. Western blot, siRNA/shRNA knockdown, IKKβ stable overexpression, pharmacological IKKβ inhibitor, IKKβ-null MEFs Biochemical and biophysical research communications Medium 19766100
2011 PKM2 directly interacts with HIF-1α and functions as a transcriptional coactivator, enhancing HIF-1 target gene transactivation by promoting p300 recruitment to HREs; PHD3 hydroxylates PKM2 at P403/P408, enhancing PKM2–HIF-1α interaction and coactivator function; this creates a positive feedback loop driving glucose metabolism reprogramming in cancer cells. Co-immunoprecipitation, ChIP, mass spectrometry (hydroxylation), anti-hydroxyproline antibody, PHD3 knockdown, metabolic assays (glucose uptake, lactate, O₂ consumption) Cell High 21620138
2011 HIF-1 directly activates RORγt transcription and forms a tertiary complex with RORγt and p300 at the IL-17 promoter to drive TH17 differentiation; concurrently HIF-1 binds Foxp3 and targets it for proteasomal degradation, attenuating Treg development; this occurs under both normoxic and hypoxic conditions. ChIP, reporter assays, co-immunoprecipitation, proteasome inhibition, HIF-1α conditional knockout mice (T cell-specific), EAE model Cell High 21871655
2012 HIF1A directly binds HRE elements in the WASF3 (WAVE3) gene promoter (demonstrated by ChIP) and activates its transcription under hypoxia, promoting cancer cell motility and invasion; WASF3 knockdown abrogates the hypoxic migratory response. ChIP, luciferase reporter assays, siRNA knockdown of WASF3, scratch wound migration assay International journal of cancer Medium 22581642
2015 Microbiota-derived butyrate drives O₂ consumption by intestinal epithelial cells, stabilizing HIF-1 and enhancing barrier function; antibiotic depletion of microbiota reduces colonic butyrate and HIF expression; butyrate effects on barrier function are lost in HIF-null cells, linking butyrate metabolism to HIF-1 stabilization. Antibiotic microbiota depletion, butyrate supplementation, germ-free mice, HIF-null cells, O₂ sensing dye assays Cell host & microbe High 25865369
2016 TIP60 (KAT5) histone acetyltransferase complex is a conserved coactivator of HIF1: HIF1A interacts with and recruits TIP60 to chromatin; TIP60 is required for HIF1A-dependent chromatin modification and RNA Pol II activation at HREs but not for HIF1A binding to target genes. Co-immunoprecipitation, ChIP-seq, genetic knockdown in Drosophila and human colorectal cancer cells, RNA Pol II ChIP Cell reports High 27320910
2017 KDM4A histone demethylase controls HIF-1α levels by removing the repressive H3K9me3 mark at the HIF1A locus; KDM4A depletion or inactivation leads to H3K9me3 accumulation at the HIF1A gene, reducing HIF-1α mRNA and protein, and decreasing hypoxic tumor-aggressive phenotypes. KDM4A siRNA knockdown, ChIP (H3K9me3 at HIF1A locus), RT-qPCR, HIF-1α protein/mRNA levels, invasion/migration assays Scientific reports Medium 28894274
2018 HIF1 binds to the PKM gene by chromatin immunoprecipitation and mediates an isoform switch from PKM1 to PKM2 after myocardial infarction, with coordinated upregulation of associated splicing factors (hnRNPA1, hnRNPA2B1, Ptbp1). Chromatin immunoprecipitation (ChIP) of HIF1 at PKM locus, RNA-seq, qRT-PCR, pyruvate kinase activity assays Physiological genomics Medium 29652636
2019 HIF-1α transcriptionally upregulates p53 by binding to five response elements in the p53 promoter under hypoxia; this HIF-1α-induced p53 is transcriptionally inactive but acts as a chaperone protein for HIF-1α, stabilizing its binding to downstream DNA response elements and increasing HIF-1 target gene synthesis. Reporter assays, ChIP, Co-immunoprecipitation, siRNA knockdown of HIF-1α, normoxia/hypoxia comparison Nucleic acids research Medium 31538203
2019 HIF1A and NFAT5 coordinately boost antibacterial defense in macrophages under high-Na⁺ conditions: HIF1A-dependent autophagy induction and NFAT5-dependent autolysosomal targeting of intracellular E. coli are both required; this defense is independent of NOS2 and phagocyte oxidase. HIF1A siRNA/genetic knockdown, NFAT5 knockdown, autophagy flux assays, bacterial CFU assays, GSEA of transcriptome Autophagy Medium 30982460
2020 HIF1a in oligodendrocyte progenitor cells (OPCs) activates non-canonical target genes (including Ascl2, Dlx3) through interaction with the OPC-specific transcription factor OLIG2; these non-canonical targets suppress Sox10 and block OPC differentiation into oligodendrocytes; MEK/ERK inhibition restores Sox10 expression without affecting canonical HIF1a activity. ChIP-seq in OPCs, OLIG2 co-IP, Ascl2/Dlx3 overexpression, Sox10 reporter assays, MEK/ERK inhibitor rescue, human oligocortical spheroids Cell stem cell High 33091368
2021 HIF-1α in cardiac fibroblasts (CFs) suppresses mitochondrial ROS to prevent excessive post-ischemic CF proliferation and scarring; CF-specific Hif-1a deletion increases mitochondrial ROS, excessive CF proliferation, and contractile dysfunction after MI; the mitochondrial-targeted antioxidant MitoTEMPO rescues Hif-1a mutant phenotypes. CF-specific Hif-1a knockout mice, MI model, scRNA-seq, 3D cardiac microtissues, MitoParaquat/MitoTEMPO pharmacological manipulation, ROS measurements Cell stem cell High 34762860
2021 m6A modification of Hif1a mRNA by FTO deficiency increases Hif1a mRNA translation via YTHDC2 recognition, elevating HIF1A protein; HIF1A then activates thermogenic gene transcription (Ppargc1a, Prdm16, Pparg), promoting white-to-beige adipocyte browning. FTO adipose-specific knockout mice, m6A-seq, RIP for YTHDC2, Hif1a KO rescue experiments, thermogenic gene expression, UCP1 assays EMBO reports High 34569703
2022 PADI4 directly interacts with and citrullinates HIF-1α at R698; this citrullination blocks VHL binding and prevents HIF-1α ubiquitination and proteasomal degradation, stabilizing HIF-1α; the PADI4 antagonist dihydroergotamine mesylate suppresses tumor progression. Co-immunoprecipitation, in vitro citrullination assay, mass spectrometry identification of citrullinated R698, VHL binding assay, ubiquitination assay, PADI4 inhibitor treatment Nature communications High 39227578
2022 Intermittent (rapid/cyclic) hypoxia increases HIF-1α protein via a distinct pathway involving KDM4A/KDM4B/KDM4C histone demethylases: intermittent hypoxia increases KDM4 activity, reduces H3K9me3 at the HIF1A locus, and increases HIF1A mRNA; this contrasts with chronic hypoxia, which decreases KDM4 activity and increases H3K9me3 globally and at the HIF1A locus. H3K9me3 ChIP at HIF1A locus, KDM4 activity assays, qRT-PCR, siRNA knockdown, comparison of intermittent vs chronic hypoxia protocols The Journal of biological chemistry Medium 36174675
2022 STAT1 is a transcriptional suppressor of HIF1A: ATG7 deficiency upregulates STAT1 via an autophagy-independent pathway (through increased ZNF148 nuclear translocation), increased STAT1 binding to HIF1A promoter, and suppressed HIF1A expression, thereby impairing ischemia-induced angiogenesis. EC-specific Atg7 KO mice, ChIP (STAT1 at HIF1A promoter), co-immunoprecipitation (ATG7-ZNF148), HIF1A overexpression rescue, fludarabine STAT1 inhibition Autophagy High 36300763
2023 USP51 deubiquitinase directly binds Elongin C (ELOC) and forms a complex with the VHL E3 ligase to deubiquitinate HIF1A, stabilizing it; HIF1A in turn transcriptionally upregulates USP51, forming a positive feedback loop; SENP1-mediated deSUMOylation of ELOC at K32 promotes USP51–ELOC interaction and HIF1A stabilization. Co-immunoprecipitation (USP51/VHL/ELOC complex), ubiquitination assay, ChIP (HIF1A binding to USP51 promoter), SUMOylation site mutagenesis (ELOC K32), in vitro deubiquitination assay Cell death and differentiation High 37816999
2023 BAP1 deubiquitylase binds HIF-1α (through its C-terminal domain residues I675, F678, I679, L691), deubiquitylates it, and stabilizes HIF-1α during hypoxia; BAP1 mutations abolishing this interaction reduce nuclear HIF-1α in mesothelioma biopsies and primary cells. Co-immunoprecipitation, computational modeling of binding interface, BAP1 mutagenesis (I675A/F678A/I679A/L691A), siRNA BAP1 knockdown, HIF-1α protein level assays in hypoxia Proceedings of the National Academy of Sciences of the United States of America High 36656861

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Targeting HIF-1 for cancer therapy. Nature reviews. Cancer 5417 13130303
1995 Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proceedings of the National Academy of Sciences of the United States of America 5108 7539918
2001 Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science (New York, N.Y.) 4644 11292861
1999 The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 4200 10353251
2001 HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science (New York, N.Y.) 3938 11292862
1996 Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Molecular and cellular biology 3206 8756616
2001 A conserved family of prolyl-4-hydroxylases that modify HIF. Science (New York, N.Y.) 2101 11598268
2005 Towards a proteome-scale map of the human protein-protein interaction network. Nature 2090 16189514
1992 A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Molecular and cellular biology 2065 1448077
2010 Hypoxia-inducible factors and the response to hypoxic stress. Molecular cell 1898 20965423
1998 Regulation of hypoxia-inducible factor 1alpha is mediated by an O2-dependent degradation domain via the ubiquitin-proteasome pathway. Proceedings of the National Academy of Sciences of the United States of America 1777 9653127
2005 Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer cell 1721 15652751
1995 Purification and characterization of hypoxia-inducible factor 1. The Journal of biological chemistry 1677 7836384
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2000 HIF-1: mediator of physiological and pathophysiological responses to hypoxia. Journal of applied physiology (Bethesda, Md. : 1985) 1430 10749844
1994 Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1. The Journal of biological chemistry 1419 8089148
2011 Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. Cell 1335 21871655
2006 Hypoxia-inducible factor-1 (HIF-1). Molecular pharmacology 1311 16887934
2000 Ubiquitination of hypoxia-inducible factor requires direct binding to the beta-domain of the von Hippel-Lindau protein. Nature cell biology 1295 10878807
2015 Crosstalk between Microbiota-Derived Short-Chain Fatty Acids and Intestinal Epithelial HIF Augments Tissue Barrier Function. Cell host & microbe 1288 25865369
2010 Network organization of the human autophagy system. Nature 1286 20562859
2002 FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes & development 1253 12080085
2002 Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch. Science (New York, N.Y.) 1247 11823643
2011 Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1. Cell 1209 21620138
1993 General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia. Proceedings of the National Academy of Sciences of the United States of America 1207 8387214
2009 A census of human transcription factors: function, expression and evolution. Nature reviews. Genetics 1191 19274049
2001 FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity. Genes & development 1173 11641274
2003 Differential roles of hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha in hypoxic gene regulation. Molecular and cellular biology 1167 14645546
2003 HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia. The EMBO journal 1137 12912907
2008 Direct regulation of TWIST by HIF-1alpha promotes metastasis. Nature cell biology 1129 18297062
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2009 HIF-1: upstream and downstream of cancer metabolism. Current opinion in genetics & development 1072 19942427
2013 HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations. The Journal of clinical investigation 1050 23999440
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2002 Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin. Molecular and cellular biology 1012 12242281
2001 HIF-1 and mechanisms of hypoxia sensing. Current opinion in cell biology 1010 11248550
2007 HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells. Cell 996 17418790
2002 HIF-1 and tumor progression: pathophysiology and therapeutics. Trends in molecular medicine 826 11927290
2007 Hypoxia-inducible factor 1 (HIF-1) pathway. Science's STKE : signal transduction knowledge environment 728 17925579
2015 HIF-1 at the crossroads of hypoxia, inflammation, and cancer. International journal of cancer 452 25784597
2009 Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization. Proceedings of the National Academy of Sciences of the United States of America 388 19805192
2005 HIF-1alpha induces genetic instability by transcriptionally downregulating MutSalpha expression. Molecular cell 288 15780936
1999 Hypoxia-induced activation of HIF-1: role of HIF-1alpha-Hsp90 interaction. FEBS letters 282 10544245
2018 Role of HIF-1 in Cancer Progression: Novel Insights. A Review. Current molecular medicine 249 30411685
2004 Intratumoral hypoxia, radiation resistance, and HIF-1. Cancer cell 197 15144945
2004 HIF-1: an oxygen and metal responsive transcription factor. Cancer biology & therapy 189 14726713
2009 Relationships between cycling hypoxia, HIF-1, angiogenesis and oxidative stress. Radiation research 188 19929412
2021 Hif-1a suppresses ROS-induced proliferation of cardiac fibroblasts following myocardial infarction. Cell stem cell 172 34762860
2001 Jab1 interacts directly with HIF-1alpha and regulates its stability. The Journal of biological chemistry 160 11707426
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 146 20392254
2007 RACK1 vs. HSP90: competition for HIF-1 alpha degradation vs. stabilization. Cell cycle (Georgetown, Tex.) 140 17361105
2004 New anticancer strategies targeting HIF-1. Biochemical pharmacology 128 15313402
2020 Metabolic Heterogeneity of Cancer Cells: An Interplay between HIF-1, GLUTs, and AMPK. Cancers 127 32252351
2004 HIF-1: master and commander of the hypoxic world. A pharmacological approach to its regulation by siRNAs. Biochemical pharmacology 118 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
2007 HIF-1 regulates hypoxia- and insulin-induced expression of apelin in adipocytes. American journal of physiology. Endocrinology and metabolism 91 17878221
2022 ALKBH5-mediated m6A modification of circCCDC134 facilitates cervical cancer metastasis by enhancing HIF1A transcription. Journal of experimental & clinical cancer research : CR 90 36028854
2005 Hypoxia and HIF-1 alpha in chondrogenesis. Seminars in cell & developmental biology 84 16144691
2016 The TIP60 Complex Is a Conserved Coactivator of HIF1A. Cell reports 83 27320910
2016 Hyperthermia induced HIF-1a expression of lung cancer through AKT and ERK signaling pathways. Journal of experimental & clinical cancer research : CR 81 27456341
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 74 27903434
2021 Flavonoids Targeting HIF-1: Implications on Cancer Metabolism. Cancers 73 33401572
2014 Hypoxia sustains glioblastoma radioresistance through ERKs/DNA-PKcs/HIF-1α functional interplay. International journal of oncology 71 24676782
2019 HIF-1 transcription activity: HIF1A driven response in normoxia and in hypoxia. BMC medical genetics 70 30808328
2021 m6A methylation promotes white-to-beige fat transition by facilitating Hif1a translation. EMBO reports 66 34569703
2018 HIF1 mediates a switch in pyruvate kinase isoforms after myocardial infarction. Physiological genomics 64 29652636
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 63 28701304
2018 Tamoxifen mechanically reprograms the tumor microenvironment via HIF-1A and reduces cancer cell survival. EMBO reports 62 30538116
2015 Modeling the interplay between the HIF-1 and p53 pathways in hypoxia. Scientific reports 60 26346319
2010 HIF-1alpha and cancer therapy. Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer 59 20033376
2019 HIF-transcribed p53 chaperones HIF-1α. Nucleic acids research 58 31538203
2008 Feminized tassels of maize mop1 and ts1 mutants exhibit altered levels of miR156 and specific SBP-box genes. Planta 57 18800226
2022 Ferroptosis-related gene NOX4, CHAC1 and HIF1A are valid biomarkers for stomach adenocarcinoma. Journal of cellular and molecular medicine 56 35023280
2022 PRMT3 drives glioblastoma progression by enhancing HIF1A and glycolytic metabolism. Cell death & disease 56 36351894
2012 Loss of fibroblast HIF-1α accelerates tumorigenesis. Cancer research 53 22556263
2018 Hypoxia-inducible transcription factors, HIF1A and HIF2A, increase in aging mucosal tissues. Immunology 52 29338076
2018 The long noncoding RNA HIF1A-AS2 facilitates cisplatin resistance in bladder cancer. Journal of cellular biochemistry 51 30216500
2016 Positive regulation of HIF-1A expression by EBV oncoprotein LMP1 in nasopharyngeal carcinoma cells. Cancer letters 51 27567526
2011 HIF-1 as a target for cancer chemotherapy, chemosensitization and chemoprevention. Current molecular pharmacology 50 20958262
2019 HIF1A and NFAT5 coordinate Na+-boosted antibacterial defense via enhanced autophagy and autolysosomal targeting. Autophagy 49 30982460
2008 HIF1 transcription factor regulates laminin-332 expression and keratinocyte migration. Journal of cell science 48 18713836
2022 HNRNPC downregulation inhibits IL-6/STAT3-mediated HCC metastasis by decreasing HIF1A expression. Cancer science 47 35848884
2020 HIF1 driven transcriptional activity regulates steroidogenesis and proliferation of bovine granulosa cells. Scientific reports 47 32127571
2002 ERK and calcium in activation of HIF-1. Annals of the New York Academy of Sciences 47 12485909
2007 The role of HIF-1 in hypoxic response in the skeletal muscle. Advances in experimental medicine and biology 46 18269201
2006 Hypoxia and HIF-1alpha in chondrogenesis. Annals of the New York Academy of Sciences 44 16831906
2004 Raising the bar: how HIF-1 helps determine tumor radiosensitivity. Cell cycle (Georgetown, Tex.) 44 15326390
2021 HIF‑1α in cerebral ischemia (Review). Molecular medicine reports 43 34878158
2020 Non-canonical Targets of HIF1a Impair Oligodendrocyte Progenitor Cell Function. Cell stem cell 43 33091368
2017 KDM4A regulates HIF-1 levels through H3K9me3. Scientific reports 43 28894274
2019 Modeling the regulation of p53 activation by HIF-1 upon hypoxia. FEBS letters 42 31282018
2017 Regulation of glycolysis in brown adipocytes by HIF-1α. Scientific reports 42 28642579
2014 Distinct microRNA expression signatures are associated with melanoma subtypes and are regulated by HIF1A. Pigment cell & melanoma research 42 24767210
2022 Cholesterol and HIF-1α: Dangerous Liaisons in Atherosclerosis. Frontiers in immunology 41 35386720
2023 USP51 facilitates colorectal cancer stemness and chemoresistance by forming a positive feed-forward loop with HIF1A. Cell death and differentiation 39 37816999
2018 Missense Variants in HIF1A and LACC1 Contribute to Leprosy Risk in Han Chinese. American journal of human genetics 39 29706348
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 36 35948068
2017 HIF1A gene polymorphisms and human diseases: Graphical review of 97 association studies. Genes, chromosomes & cancer 36 28165644
2016 BP-1T, an antiangiogenic benzophenone-thiazole pharmacophore, counteracts HIF-1 signalling through p53/MDM2-mediated HIF-1α proteasomal degradation. Angiogenesis 36 27743086
2019 Improved Motor Nerve Regeneration by SIRT1/Hif1a-Mediated Autophagy. Cells 35 31671642
2007 MgcRacGAP interacts with HIF-1alpha and regulates its transcriptional activity. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 34 17982282
2018 The p38α Stress Kinase Suppresses Aneuploidy Tolerance by Inhibiting Hif-1α. Cell reports 33 30332653
2020 Independence of HIF1a and androgen signaling pathways in prostate cancer. BMC cancer 32 32450824
2019 Transferrin receptor-involved HIF-1 signaling pathway in cervical cancer. Cancer gene therapy 32 30651591
2016 Downregulation of HIF-1a sensitizes U251 glioma cells to the temozolomide (TMZ) treatment. Experimental cell research 32 27090014
2014 Neuroprotective effect of pAkt and HIF-1 α on ischemia rats. Asian Pacific journal of tropical medicine 32 24507644
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
2023 NPAS2 promotes aerobic glycolysis and tumor growth in prostate cancer through HIF-1A signaling. BMC cancer 30 36978001
2022 HIF-1α protects osteoblasts from ROS-induced apoptosis. Free radical research 29 35380485
2022 Pharmacological inhibition of sphingolipid synthesis reduces ferroptosis by stimulating the HIF-1 pathway. iScience 27 35784791
2018 Adverse effects of Hif1a mutation and maternal diabetes on the offspring heart. Cardiovascular diabetology 27 29753320
2022 Ablation of endothelial Atg7 inhibits ischemia-induced angiogenesis by upregulating Stat1 that suppresses Hif1a expression. Autophagy 26 36300763
2021 Single-cell transcriptomic identified HIF1A as a target for attenuating acute rejection after heart transplantation. Basic research in cardiology 26 34870762
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 25 28366537
2009 TNFalpha induces HIF-1alpha expression through activation of IKKbeta. Biochemical and biophysical research communications 25 19766100
2024 Citrullination modulation stabilizes HIF-1α to promote tumour progression. Nature communications 24 39227578
2006 Leukocyte's Hif-1 expression and training-induced erythropoietic response in swimmers. Medicine and science in sports and exercise 24 16888453
2023 BAP1 is a novel regulator of HIF-1α. Proceedings of the National Academy of Sciences of the United States of America 23 36656861
2023 Hypoxia-Induced Autophagy Is Involved in Radioresistance via HIF1A-Associated Beclin-1 in Glioblastoma Multiforme. Heliyon 23 36691538
2023 FSHR-mTOR-HIF1 signaling alleviates mouse follicles from AMPK-induced atresia. Cell reports 23 37733588
2022 Baicalein Inhibits the Progression and Promotes Radiosensitivity of Esophageal Squamous Cell Carcinoma by Targeting HIF-1A. Drug design, development and therapy 23 35937565
2022 Intermittent hypoxia enhances the expression of hypoxia inducible factor HIF1A through histone demethylation. The Journal of biological chemistry 23 36174675
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