Affinage

HES1

Transcription factor HES-1 · UniProt Q14469

Length
280 aa
Mass
29.5 kDa
Annotated
2026-06-10
100 papers in source corpus 41 papers cited in narrative 41 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HES1 is a basic helix-loop-helix transcriptional repressor that operates as the principal downstream effector of Notch signaling, governing the balance between progenitor maintenance and differentiation across neural, pancreatic, hematopoietic, and muscle lineages (PMID:10205173, PMID:9819428, PMID:10774739). Delta-1 engagement of Notch-1 drives RBP-J (CSL)-dependent transcriptional induction of HES1, and HES1 together with HES5 is genetically required for Notch to block neuronal differentiation (PMID:10205173, PMID:9819428). The canonical output of HES1 is repression of proneural/pro-differentiation bHLH factors such as Mash1/Ascl1, which keeps precursor cells undifferentiated and, when lost, causes premature differentiation and progenitor depletion in multiple tissues (PMID:10615124, PMID:10774739, PMID:16728479, PMID:30862661). HES1 sustains progenitor proliferation by directly repressing cell-cycle inhibitors — p27Kip1, p57, p21/Cip1, and E2F-1 — through binding to class C/CACGAG sites in their promoters (PMID:15467735, PMID:15870295, PMID:16513761, PMID:16899237). A defining feature of HES1 is that its expression oscillates with ~2-hour periodicity generated by transcriptional time-delay negative autoregulation, and these oscillations are functionally distinct from sustained high-level expression: oscillatory HES1 keeps Ascl1 (and MyoD) suppressed to promote stem-cell proliferation and quiescence exit, whereas persistent high-level HES1 enforces sustained Ascl1 repression, quiescence, or boundary (neuron-free) identity (PMID:12932324, PMID:16728479, PMID:30862661, PMID:30862660, PMID:32094111, PMID:34703994). HES1 protein levels are set by ubiquitin/proteasome turnover, antagonized by the deubiquitinases Usp27x/Usp22/Usp51 and promoted by RASSF1A-scaffolded SNURF/RNF4-mediated degradation (PMID:25846153, PMID:34897944). Beyond progenitor control, HES1 restrains inflammatory and innate-immune responses, blocking P-TEFb-dependent transcription elongation at Cxcl1 and, atypically acting as an activator, inducing VEGF-C to suppress the TLR adaptor WDFY1 (PMID:27322654, PMID:31015298). HES1 expression is additionally tuned by non-Notch inputs including JNK, oncogenic KRAS/MAPK-ERK, Stat3, CREB/Sirt-1, and the aryl hydrocarbon receptor (PMID:14722248, PMID:16732296, PMID:17592117, PMID:26804914, PMID:30705405).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 1994 Medium

    Establishing the human HES1 gene structure and chromosomal location provided the molecular foundation for studying it as a conserved bHLH factor.

    Evidence Genomic cloning, sequencing, and FISH mapping of human HRY/HES1

    PMID:8020957

    Open questions at the time
    • Does not address function or regulation
    • No protein interaction or target data
  2. 1998 High

    Defining HES1 as a direct transcriptional target of the Delta/Notch/RBP-J axis answered how Notch signal is converted into a transcriptional output.

    Evidence Two-cell coculture with HES1 promoter-luciferase reporter, endogenous mRNA measurement, and dominant-negative Kuzbanian/RBP-J inhibition

    PMID:9819428

    Open questions at the time
    • Does not show which downstream genes HES1 then regulates
    • Cell-type generality of RBP-J dependence not tested
  3. 1999 High

    Genetic epistasis placed HES1/HES5 downstream of Notch as obligatory effectors, showing Notch cannot block neuronal differentiation without them.

    Evidence Constitutively active Notch misexpression in Hes1/Hes5 single- and double-null neural precursors

    PMID:10205173

    Open questions at the time
    • Direct DNA targets mediating the block not defined here
    • Redundancy with other HES/HEY factors not fully resolved
  4. 1999 Medium

    Demonstrating that a non-DNA-binding HES-1 mutant still represses MASH-1 revealed a DNA-binding-independent mode of repression alongside its canonical promoter binding.

    Evidence Retroviral HES-1/MASH-1 expression with non-DNA-binding mutant in hippocampal neurons and reporter assays

    PMID:10336252

    Open questions at the time
    • Molecular basis of DNA-binding-independent repression unresolved
    • Relative contribution of each mode in vivo unknown
  5. 2000 High

    Loss- and gain-of-function across multiple tissues established HES1 as a general repressor of proneural/endocrine bHLH factors that keeps precursors undifferentiated.

    Evidence Hes1 knockout mice with histology/expression analysis in pancreas, gut, brain, eye, thymus and misexpression studies

    PMID:10615124 PMID:10774739

    Open questions at the time
    • Direct vs indirect target regulation not fully separated
    • Mechanism of repression at each target undefined at this stage
  6. 2000 High

    Identifying Hes6 as a HES1 antagonist and mapping the loop region defined how HES1 repressive activity itself is modulated.

    Evidence DNA-binding/reporter assays, retinal retroviral misexpression, and loop-region domain swaps

    PMID:10851137

    Open questions at the time
    • Structural basis of Hes6 inhibition not resolved
    • In vivo physiological relevance limited to retina
  7. 2004 High

    Defining HES1 control of E2F-1 and adipogenic regulators (C/EBPalpha, PPARgamma2, DLK/Pref-1) connected HES1 repression directly to cell-cycle entry and lineage commitment.

    Evidence Inducible/dominant-negative HES1, promoter-reporter with site mutation, and Jagged1/Hes1 gain- and loss-of-function with rescue in 3T3-L1 cells

    PMID:15060169 PMID:15467735

    Open questions at the time
    • Direct promoter binding to adipogenic genes not all demonstrated
    • Tissue specificity of the E2F-1 axis untested
  8. 2004 Medium

    Discovery that AhR transcriptionally induces HES1, with HES1 repressing its own AhR-driven transcription, introduced a non-Notch input and an autoregulatory loop.

    Evidence Promoter-reporter assays with XRE/HES composite element identification and protein competition assays

    PMID:14722248

    Open questions at the time
    • Physiological context of AhR-HES1 loop not established in vivo
    • Single-lab reporter-based evidence
  9. 2005 High

    ChIP-level evidence that HES1 directly represses p27Kip1 explained mechanistically how HES1 promotes progenitor proliferation.

    Evidence Inducible Hes1, p27Kip1 promoter-reporter, ChIP, and Hes1-null tissue analysis

    PMID:15870295

    Open questions at the time
    • Whether p27 repression is sufficient for proliferation control not isolated
    • Interplay with other CDK inhibitor targets not addressed here
  10. 2006 High

    Extending direct repression to p57 (with double-knockout epistasis), p21, and demonstrating boundary-cell roles unified HES1 control of progenitor self-renewal and organizer identity.

    Evidence Hes1/p57 and Hes1/Hes3/Hes5 compound knockouts, DNA-binding-domain-dependent HSC assays, and persistent Hes1 misexpression

    PMID:16513761 PMID:16728479 PMID:16899237

    Open questions at the time
    • Quantitative contribution of each CDK inhibitor target differs by tissue
    • How sustained vs dynamic expression dictates boundary vs progenitor fate not yet mechanistically defined
  11. 2006 Medium

    Identifying JNK-driven, Notch-independent HES1 induction in confluent endothelium broadened the regulatory inputs beyond the canonical pathway.

    Evidence Proliferating vs confluent endothelial comparison with pharmacological JNK inhibition and Western blot

    PMID:16732296

    Open questions at the time
    • Direct JNK-to-HES1 transcriptional mechanism not mapped
    • Pharmacological inhibition only; limited mechanistic depth
  12. 2007 Medium

    Mathematical modeling plus identification of Id-protein and Stat3 inputs explained how the HES1 oscillator is generated and how its autoregulation and protein half-life are tuned.

    Evidence Delay differential equation modeling constrained by half-life data; Id2 Co-IP with loss/gain-of-function; serum-induced Stat3 oscillation and Hes1 half-life measurement

    PMID:12932324 PMID:17592117 PMID:17681138

    Open questions at the time
    • Modeling lacks direct experimental perturbation of the delay
    • How Id and Stat3 inputs integrate quantitatively not resolved
  13. 2008 Medium

    Demonstration that HES1 directly represses 5-HT1A and (later) GABAB1 receptor genes extended its repressor role to neurotransmitter-receptor programming.

    Evidence Promoter-reporter with consensus-site mutation, HES1-null receptor expression analysis, and ChIP at GABAB1 promoter with behavioral readouts

    PMID:18499474 PMID:35732696

    Open questions at the time
    • Behavioral consequences mechanistically indirect
    • Allele-selectivity and receptor specificity incompletely generalized
  14. 2012 High

    Mapping GATA-1/Ikaros recruitment of NuRD and PRC2/EZH2 to the Hes1 locus revealed how HES1 itself is epigenetically silenced during lineage commitment.

    Evidence ChIP of GATA-1, FOG-1, MI-2, GFI1B, and EZH2 at the Hes1 locus in erythroid cells with EZH2 requirement assays

    PMID:22778136

    Open questions at the time
    • Whether this repressive module operates outside erythroid cells unknown
    • Dynamics relative to oscillation not addressed
  15. 2015 High

    Identifying deubiquitinase (Usp22/Usp27x/Usp51) control of HES1 stability connected protein turnover directly to oscillation period and differentiation timing.

    Evidence HES1 antibody pulldown for DUB purification, deubiquitination assays, Usp22 knockdown with half-life/oscillation measurement, and in vivo Usp27x misexpression

    PMID:25846153

    Open questions at the time
    • E3 ligase(s) opposing these DUBs not identified here
    • Tissue-specific DUB usage not mapped
  16. 2015 Medium

    Identifying HES1 repression of BBC3/PUMA and interaction with PARP1 showed HES1 contributes to leukemic survival and revealed a cell-type-specific cytotoxic vulnerability.

    Evidence HES1 knockdown with ChIP at BBC3 and apoptosis assays in T-ALL; reciprocal HES1-PARP1 Co-IP with NAD+/ATP/AIF readouts in B-ALL

    PMID:21224467 PMID:25784680

    Open questions at the time
    • Why PARP1 engagement is B-ALL-specific not fully explained
    • BBC3 finding from single lab with knockdown only
  17. 2016 High

    Discovery of elongation-based (P-TEFb) repression at Cxcl1 and activator function inducing VEGF-C/WDFY1 established HES1 roles in restraining inflammation and innate immunity by non-canonical mechanisms.

    Evidence Hes1-null macrophages with ChIP for P-TEFb/Pol II Ser2; genome-wide ChIP-seq with VEGF-C/WDFY1 assays in infection and lupus models

    PMID:27322654 PMID:31015298

    Open questions at the time
    • How HES1 switches between repressor and activator modes unresolved
    • Direct vs indirect VEGF-C activation mechanism not fully dissected
  18. 2018 High

    Demonstrating direct HES1 repression of GADD34 linked HES1 to cytoprotection during ER stress.

    Evidence HES1 depletion with ChIP at GADD34 promoter and GADD34-dependent cell-death assays in mouse and human cells

    PMID:29491143

    Open questions at the time
    • Upstream signal controlling HES1 during ER stress not defined
    • Relationship to oscillation dynamics unknown
  19. 2019 High

    Live-imaging of oscillation dynamics in neural and muscle stem cells established the functional distinction between oscillatory and sustained HES1 in driving proliferation versus quiescence/differentiation.

    Evidence Hes1/Ascl1 and Hes1/MyoD reporter live imaging with conditional knockout and sustained overexpression in adult NSCs and muscle stem cells

    PMID:30862660 PMID:30862661

    Open questions at the time
    • Molecular machinery sensing oscillatory vs sustained dynamics unknown
    • How downstream effectors decode HES1 frequency unresolved
  20. 2019 High

    Showing KRAS/MAPK-ERK-driven sustained HES1 is required for ADM-to-PanIN progression, and that HES1 potentiates hedgehog signaling, expanded HES1 roles into oncogenic and ciliary contexts.

    Evidence Conditional Hes1 ablation in KrasG12D pancreatic models with lineage tracing; epithelial Hes1 knockout with ciliogenesis and Smoothened rescue in hair follicle stem cells

    PMID:30705405 PMID:31721388

    Open questions at the time
    • Direct HES1 targets driving PanIN progression not specified
    • Mechanism of HES1 control over ciliary Smoothened accumulation unclear
  21. 2020 High

    Defining HES1 control of HSC metabolism (PPARgamma/FAO) and the quantitative requirement for robust oscillation amplitude refined how HES1 enforces quiescence and proper neurogenic timing.

    Evidence Hes1 conditional knockout HSC transplantation with FAO/PPARgamma pharmacological rescue; type-1/type-2 oscillation knock-in alleles with brain morphometry and proliferation/apoptosis assays

    PMID:32094111 PMID:32129527

    Open questions at the time
    • Direct HES1 target in the PPARgamma/FAO axis not identified
    • How amplitude is read out by progenitors unknown
  22. 2021 Medium

    Identifying RASSF1A/SNURF-RNF4-mediated degradation and showing oscillation is specifically required for quiescence exit completed a stability-and-dynamics regulatory picture with tumor and stem-cell consequences.

    Evidence RASSF1A-HES1-SNURF/RNF4 Co-IP and ubiquitination assays with stability measurement; matched-level persistent vs oscillatory HES1 in BMP4-induced quiescent NSCs

    PMID:34703994 PMID:34897944

    Open questions at the time
    • How SUMO-targeted degradation integrates with DUB activity unresolved
    • Quiescence-exit finding is single-lab
  23. 2022 Medium

    Identifying HES1 activator targets IGBP1/PP6 (in psoriasis) and MYEOV/SOX9-driven HES1 induction added activator functions and upstream transcriptional regulators in disease contexts.

    Evidence ChIP at IGBP1 promoter with PP6 ubiquitination and HES1 stability assays; MYEOV-SOX9 Co-IP and ChIP at HES1 enhancer with knockdown rescue

    PMID:32879444 PMID:36535970

    Open questions at the time
    • Determinants of HES1 activator vs repressor behavior unresolved
    • Single-lab evidence for each axis
  24. 2023 Medium

    Dissecting dynamics-dependent p21 control (Dusp7/p-Erk) and metabolic reprogramming via IGF2BP2/GLUT1 showed HES1 output depends on its expression mode and reaches into glycolytic metabolism.

    Evidence Oscillatory vs sustained Hes1 in NSCs with Dusp7/p-Erk/p21 readouts; HES1 ChIP at IGF2BP2 promoter with GLUT1 mRNA stability and glycolysis assays

    PMID:37200191 PMID:37957183

    Open questions at the time
    • Generality of the dynamics-dependent paradoxical p21 effect untested
    • Metabolic axis demonstrated mainly in colorectal cancer cells

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how the molecular machinery distinguishes oscillatory from sustained HES1 and how HES1 switches between transcriptional repressor and activator modes at different loci.
  • No mechanism linking oscillation frequency/amplitude to target decoding
  • No structural or cofactor basis explaining activator vs repressor switching
  • Opposing E3 ligase/DUB balance across tissues incompletely mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 6
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-1640170 Cell Cycle 5 R-HSA-1266738 Developmental Biology 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-162582 Signal Transduction 2 R-HSA-168256 Immune System 2
Partners
HES6ID2PARP1RASSF1ARBPJRNF4USP22

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Hes1 and Hes5 are essential downstream effectors of Notch signaling in mammalian neuronal differentiation; constitutively active Notch fails to inhibit neuronal differentiation in Hes1/Hes5 double-null neural precursor cells, placing Hes1 genetically downstream of Notch in this pathway. Retroviral misexpression of constitutively active Notch in wild-type, Hes1-null, Hes5-null, and Hes1/Hes5 double-null mouse neural precursor cells; genetic epistasis The EMBO journal High 10205173
1998 Delta-1 activation of Notch-1 results in transcriptional upregulation of HES-1; this transactivation requires both Kuzbanian metalloprotease activity and RBP-J (CSL) transcription factor activity, placing HES-1 as a direct transcriptional target downstream of the Delta-1/Notch-1/RBP-J axis. Two-cell coculture assay with Notch-1-expressing cells and Delta-1-expressing cells; HES-1 promoter-luciferase reporter; endogenous HES-1 mRNA measurement; dominant-negative Kuzbanian and RBP-J inhibition Molecular and cellular biology High 9819428
2000 Hes1 deficiency in mice causes depletion of pancreatic epithelial precursors through accelerated differentiation into endocrine cells, with upregulation of multiple bHLH proneural/endocrine factors, establishing Hes1 as a general negative regulator of endodermal endocrine differentiation that keeps precursor cells undifferentiated. Hes1 knockout mouse analysis; histology; expression analysis of bHLH components in pancreas, stomach and gut Nature genetics High 10615124
2000 Hes6 suppresses Hes1 transcriptional repression without itself binding DNA; Hes6 also relieves Hes1-mediated inhibition of Mash1-E47 heterodimer transcriptional activity. Loop-region swapping between Hes1 and Hes6 partially exchanges their specific functions, indicating the loop region is functionally important. DNA binding assays; transcriptional reporter assays; retroviral misexpression in developing retina; domain-swap mutagenesis Development (Cambridge, England) High 10851137
2000 Hes1 functions as a bHLH transcriptional repressor that antagonizes positive bHLH factors (e.g., Mash1); misexpression of Hes1 inhibits differentiation and maintains precursor/proliferative state, while loss of Hes1 leads to upregulation of positive bHLH genes and premature differentiation across multiple tissues (brain, eye, pancreas, thymus). Hes1 knockout mouse model; Hes1 misexpression experiments; expression analysis of downstream bHLH targets Molecules and cells High 10774739
2003 Mathematical modeling demonstrates that the observed ~2-hour oscillatory expression of Hes1 mRNA and protein is driven by transcriptional time delays inherent in the negative autoregulatory feedback loop of Hes1; oscillation period is determined by the delay and the protein/mRNA half-lives. Mathematical modeling of delay differential equations constrained by experimental mRNA and protein half-life data Current biology : CB Medium 12932324
2004 Hes-1 directly represses E2F-1 transcription through a CACGAG site in the E2F-1 promoter, inhibiting G1/S-phase transition and estrogen/heregulin-beta1-stimulated proliferation in breast cancer cells. Tetracycline-regulated HES-1 expression; dominant-negative HES-1; luciferase reporter with E2F-1 promoter and CACGAG site mutation; cell cycle analysis Oncogene High 15467735
2004 HES-1 is a novel transcriptional target of the aryl hydrocarbon receptor (AhR); AhR and HES-1 protein compete for binding to a composite HES/XRE element at -48/-42 in the HES-1 promoter, establishing a negative autoregulatory loop where HES-1 represses its own AhR-induced transcription. Actinomycin D transcription inhibition; luciferase reporter with HES-1 promoter; identification and mutation of XRE/HES composite element; protein competition assays Molecular pharmacology Medium 14722248
2004 Notch/Hes-1 signaling blocks adipogenesis by suppressing C/EBPalpha and PPARgamma2 induction; constitutive Hes-1 expression mimics Jagged1-induced differentiation block, which can be rescued by ectopic C/EBPalpha or PPARgamma2. Additionally, Hes-1 down-regulates DLK/Pref-1 transcription, revealing a dual role in adipocyte development. Notch ligand (Jagged1) exposure of 3T3-L1 cells; retroviral Hes-1 expression; siRNA knockdown of Hes-1; retroviral rescue with C/EBPalpha and PPARgamma2 Molecular and cellular biology High 15060169
2005 Hes1 directly promotes progenitor cell proliferation by transcriptionally repressing the cyclin-dependent kinase inhibitor p27Kip1 through binding to class C sites in the p27Kip1 promoter; Hes1-deficient mouse tissues show elevated p27Kip1 transcripts. Tetracycline-inducible Hes1 expression; p27Kip1 promoter-reporter assays; chromatin immunoprecipitation; retinoic acid-induced Hes1 repression model; Hes1-null mouse tissue analysis Molecular and cellular biology High 15870295
2006 Persistent and high-level Hes1 expression constitutively represses proneural bHLH gene (Mash1) expression in boundary cells of the developing CNS, forming neuron-free organizing centers; loss of Hes1/Hes3/Hes5 causes ectopic proneural gene expression and neurogenesis at boundaries. Hes1/Hes3/Hes5 compound knockout mice; retroviral persistent Hes1 expression in neural progenitors; in situ hybridization for Hes1 and Mash1 Development (Cambridge, England) High 16728479
2006 HES1 inhibits hematopoietic progenitor cell cycling in a manner requiring its DNA-binding domain; HES1 overexpression upregulates p21(Cip1/Waf1) and inhibits cell expansion without inducing apoptosis or altering differentiation, while preserving long-term HSC reconstituting activity. Lentiviral overexpression of wild-type HES1 vs. DNA-binding domain deletion mutant (BHES1) in human CD34+ and mouse HSCs; in vitro cycling assays; in vivo repopulation assays Stem cells (Dayton, Ohio) High 16513761
2006 Hes1 directly represses p57 transcription in pancreatic progenitors to maintain their cell cycle progression; Hes1 inactivation upregulates p57, causing cell cycle arrest and precocious differentiation. p57/Hes1 double-null embryos show expanded progenitor populations, confirming that p57 is a direct Hes1 target mediating progenitor self-renewal. Hes1 knockout mice; p57/Hes1 double knockout mice; expression analysis; genetic epistasis Developmental biology High 16899237
2006 Hes-1 expression is elevated in confluent endothelial cells through a Notch-independent mechanism involving c-Jun N-terminal kinase (JNK) signaling, demonstrating that HES-1 can be regulated by a non-Notch pathway. Comparison of Notch activation levels vs. Hes-1 protein in proliferating vs. confluent endothelial cells; pharmacological JNK inhibition; Western blot Laboratory investigation Medium 16732296
2007 Stat3 oscillations, induced by serum, drive oscillatory Hes1 expression by regulating Hes1 protein half-life; coupled Stat-Hes1 oscillations are required for efficient G1 cell cycle progression and cell proliferation. Serum stimulation assays; identification of Stat3/Smad1 oscillations with their inhibitors Socs3/Smad6; Hes1 protein half-life measurements; loss of Hes1 oscillation with G1 phase analysis Proceedings of the National Academy of Sciences of the United States of America Medium 17592117
2007 Id proteins directly interact with Hes1 protein and release its negative autoregulatory feedback (self-repression) without interfering with Hes1 repression of other target genes, thereby sustaining Hes1 expression levels in early neural tube and maintaining neural stem cell pools. Co-immunoprecipitation of Id2 with Hes1; Id2 overexpression in chick hindbrain; Id1/Id3 double knockout mice; Id1-3 RNAi in chick embryos; Hes1 expression analysis Developmental cell High 17681138
2008 HES1 directly represses 5-HT1A receptor transcription through a HES consensus site in the promoter; HES1 represses at both C(-1019) and G(-1019) alleles (unlike HES5 which is allele-selective). Loss of HES1 in knockout mice elevates 5-HT1A receptor expression in E12.5 hindbrain and midbrain, confirming HES1 is required for correct developmental 5-HT1A expression. HES1 promoter-reporter assays with consensus site mutation; HES1 overexpression and HES6 co-expression experiments; HES1-/- mouse 5-HT1A expression analysis Molecular and cellular neurosciences High 18499474
2011 HES1 directly interacts with PARP1 in B-cell ALL; HES1-PARP1 interaction inhibits HES1 transcriptional function and activates PARP1, leading to PARP1 auto-ADP-ribosylation, NAD+ consumption, ATP depletion, and apoptosis-inducing factor nuclear translocation, causing apoptosis specifically in B-ALL but not T-ALL. Co-immunoprecipitation of HES1 and PARP1; PARP1 activation assays; NAD+/ATP measurements; AIF nuclear translocation assay; cell viability in B-ALL vs. T-ALL Blood High 21224467
2012 GATA-1, facilitated by Ikaros, directly represses Hes1 gene expression in erythroid cells by recruiting FOG-1, NuRD/MI-2 ATPase, GFI1B, and the Polycomb repressive complex 2 (PRC2/EZH2) to the Hes1 locus; EZH2-mediated H3K27 methylation is required for transient Hes1 repression during erythroid differentiation. RNAi depletion of HES1 in mouse erythroleukemia cells; Ikaros-deficient mouse erythroid cells; ChIP for GATA-1, FOG-1, MI-2, GFI1B, EZH2 at Hes1 locus; EZH2 requirement assays Molecular and cellular biology High 22778136
2013 Hes1 directly binds to the promoter region of the FLT3 gene and represses its transcription; Hes1 deletion in MLL-AF9 leukemia cells upregulates FLT3, enhances FLT3L-stimulated ERK phosphorylation and proliferation, and FLT3 inhibition reverses Hes1-null AML cell proliferation. ChIP of Hes1 at FLT3 promoter; FLT3 promoter-reporter assays; Hes1 knockout in MLL-AF9 AML model; ERK phosphorylation assays; FLT3 inhibitor treatment Leukemia High 25234168
2015 HES1 directly represses BBC3 (encoding the pro-apoptotic PUMA) in T-ALL cells, thereby promoting tumor cell survival downstream of NOTCH1 signaling. HES1 knockdown in T-ALL; BBC3/PUMA expression analysis; functional apoptosis assays; ChIP at BBC3 locus Blood Medium 25784680
2015 Ubiquitin-specific proteases Usp27x, Usp22, and Usp51 deubiquitinate and stabilize Hes1 protein; Usp22 knockdown shortens Hes1 half-life, delays Hes1 oscillations, and enhances neuronal differentiation in developing mouse brain, while Usp27x misexpression reduces neuronal differentiation. Hes1-specific antibody pulldown from mouse ES cells for deubiquitinase purification; deubiquitination assays; Usp22 knockdown (protein half-life, oscillation period measurement); Usp27x misexpression in developing brain The FEBS journal High 25846153
2016 Hes1 suppresses inflammatory gene expression (specifically Cxcl1) by inhibiting recruitment of the positive transcription-elongation complex P-TEFb to the Cxcl1 locus, thereby preventing RNA Pol II Ser2 phosphorylation and productive elongation — a post-initiation mechanism distinct from typical pre-initiation transcriptional repression. Hes1 knockout macrophages; in vivo neutrophil recruitment assays; ChIP for P-TEFb and RNA Pol II Ser2 phosphorylation at Cxcl1; inflammatory arthritis model Nature immunology High 27322654
2016 Hes1 attenuates type I IFN production not by directly repressing IFN genes, but by transcriptionally activating VEGF-C expression (a rare case of Hes1 acting as a transcriptional activator); VEGF-C induction suppresses the TLR upstream adaptor WDFY1, thereby dampening TLR signaling and IFN production. Hes1-deficient mice; genome-wide Hes1 ChIP-seq; VEGF-C and WDFY1 expression assays; ENCEPHALOMYOCARDITIS virus infection model; lupus nephritis model The Journal of experimental medicine High 31015298
2016 CREB and Sirt-1 cooperatively regulate Hes1 promoter activity in neural stem cells in response to glucose availability: excess glucose promotes Sirt-1-dependent repression of the Hes1 promoter, while low glucose favors CREB replacement of Sirt-1 at Hes1 chromatin, enhancing Hes1 expression and proliferation. CREB-deficient NSCs; glucose manipulation; ChIP for CREB and Sirt-1 at Hes1 promoter; Hes1 promoter-reporter assays; NSC proliferation assays Cell reports High 26804914
2018 Hes1 directly binds the GADD34 promoter and represses GADD34 expression during ER stress, protecting cells from apoptosis; HES1 depletion increases GADD34 expression and cell death during ER stress in a GADD34-dependent manner. HES1 depletion (siRNA/shRNA) in mouse and human cells; ChIP of HES1 at GADD34 promoter; GADD34 expression measurement; cell death assays with GADD34 dependency The Journal of biological chemistry High 29491143
2019 In quiescent adult neural stem cells, Hes1 oscillates at higher levels than in active NSCs, keeping Ascl1 continuously suppressed; inactivation of Hes1 and related genes upregulates Ascl1 and increases neurogenesis causing NSC depletion, while sustained Hes1 overexpression represses Ascl1 and maintains quiescence. Hes1 conditional knockout mice (with Hes3/Hes5 compound deletion); live imaging of Hes1-Venus and Ascl1-Venus reporters in adult brain NSCs; sustained Hes1 overexpression; Ascl1 oscillation induction Genes & development High 30862661
2019 Hes1 oscillates in activated muscle stem cells and drives oscillatory MyoD expression; ablation of the Hes1 oscillator disrupts MyoD oscillations, leads to sustained MyoD expression and premature differentiation, impairing muscle stem cell maintenance and muscle growth/repair. Live imaging of Hes1 and MyoD reporters in dispersed cells, single muscle fiber cultures, and muscle biopsies; conditional Hes1 ablation; muscle regeneration assays Genes & development High 30862660
2019 Mutant KRAS-induced sustained Hes1 expression (via MAPK/ERK signaling) is required for acinar-to-ductal metaplasia (ADM) to progress to pancreatic intraepithelial neoplasia (PanIN); Hes1 ablation in KrasG12D mice forces ADM to re-differentiate back to acinar cells and prevents PDAC formation. Elastase1-CreERT2;KrasG12D mouse model with Hes1 genetic ablation; KrasG12D;Trp53R172H;Hes1-null PDAC model; gene expression analysis; lineage tracing Oncogene High 30705405
2019 Epithelial Hes1 deletion modulates ciliogenesis and Smoothened ciliary accumulation in response to Shh; Hes1 potentiates hedgehog signaling in hair follicle stem cells to enable anagen initiation and HFSC self-renewal during repetitive depilation. Epithelial Hes1 conditional knockout mice; microarray gene profiling of HFSCs; primary keratinocyte ciliogenesis assays; Smoothened agonist rescue experiments Stem cells (Dayton, Ohio) Medium 31721388
2020 Hes1 deficiency in hematopoietic cells leads to HSC exhaustion under replicative stress by upregulating PPARgamma signaling and augmenting fatty acid oxidation (FAO); PPARgamma targeting or FAO inhibition rescues repopulating defects of Hes1-null HSCs by restoring quiescence. Hes1-flox/Vav1-Cre conditional knockout mice; bone marrow transplantation/stress hematopoiesis assays; transcriptome analysis; FAO measurement; pharmacological PPARgamma and FAO inhibition Stem cells (Dayton, Ohio) High 32129527
2020 Robust Hes1 oscillations (high amplitude) are required for normal NPC proliferation and correct timing of neurogenesis; knock-in mice with dampened Hes1 oscillations (type-1 mutation) display smaller brains, decreased NPC proliferation, increased cell death, and upregulated proneural genes, while elongated-period (type-2) mutants are normal. Hes1 knock-in mice with shortened (type-1) and elongated (type-2) oscillation periods; brain morphometry; EdU proliferation assays; TUNEL apoptosis assays; proneural gene expression analysis Development (Cambridge, England) High 32094111
2021 RASSF1A acts as a scaffold for the SUMO-targeted E3 ubiquitin ligase SNURF/RNF4 to target HES1 for proteasomal degradation; RASSF1A loss stabilizes HES1 protein, promoting tumor dedifferentiation, independently of RASSF1A's role in the Hippo pathway. Co-immunoprecipitation of RASSF1A with HES1 and SNURF/RNF4; ubiquitination assays; proteasome inhibition; RASSF1A depletion with HES1 protein stability measurement; GSI sensitivity assays EMBO reports High 34897944
2021 HES1 oscillatory expression is specifically required for neural stem cells to exit quiescence; persistent (non-oscillatory) HES1 expression at physiological levels does not affect entry into quiescence or proliferation but specifically impedes quiescence exit. BMP4-induced quiescence in embryonic NSCs; persistent HES1 expression under moderate-strength promoter to override oscillations while maintaining total level; cell cycle and quiescence exit assays iScience Medium 34703994
2022 In the medial prefrontal cortex, Hes1 directly binds to the GABAB1 receptor promoter and represses its transcription; Notch1-Hes1 signaling negatively regulates GABAB1 receptor expression and thereby modulates neuronal activity in methamphetamine-induced psychosis. ChIP of Hes1 at GABAB1 receptor promoter; Notch1 genetic and pharmacological manipulation; GABAB1 receptor expression and behavioral assays Molecular psychiatry Medium 35732696
2022 HES1 transcriptionally activates immunoglobulin-binding protein 1 (IGBP1) expression, which in turn promotes protein phosphatase 6 (PP6) expression and inhibits its ubiquitination; this HES1-IGBP1-PP6 axis is dysfunctional in psoriasis, and L-menthol upregulates HES1 by preventing its proteasomal degradation. Target identification screen with L-menthol; ChIP of HES1 at IGBP1 promoter; HES1 knockdown/overexpression; PP6 ubiquitination assays; HES1 protein stability assays Nature communications Medium 36535970
2023 Oscillatory Hes1 expression directly represses p21 (Cdkn1a) to promote NSC proliferation; however, sustained Hes1 overexpression paradoxically upregulates p21 by repressing Dusp7 (a phosphatase for p-Erk) and increasing p-Erk levels, which indirectly elevates p21. Thus, Hes1 differentially controls cell proliferation depending on its expression dynamics. Oscillatory vs. sustained Hes1 expression in mouse NSCs; p21 expression measurement; Dusp7 expression analysis; p-Erk level measurement; proliferation assays Cell reports Medium 37200191
1994 The human HES1 gene (HRY) encodes a bHLH protein with only four amino acid differences from the rat homolog; the coding region is contained within four exons; the locus was mapped by FISH to chromosome 3q28-q29. Genomic cloning; sequence analysis; fluorescence in situ hybridization (FISH) Genomics Medium 8020957
1999 Forced HES-1 expression in hippocampal neurons inhibits intrinsic and NGF-induced neurite outgrowth and blocks MASH-1-activated differentiation; even a non-DNA-binding mutant of HES-1 retains the ability to repress MASH-1-dependent transcription, indicating a DNA-binding-independent repression mechanism. Retroviral HES-1 and MASH-1 expression in TrkA-transfected hippocampal neurons; NGF-induced differentiation assay; non-DNA-binding HES-1 mutant co-expression; reporter assays Journal of neuroscience research Medium 10336252
2020 MYEOV interacts directly with SOX9 in the nucleus and enhances SOX9 DNA-binding ability to the HES1 enhancer, promoting HES1 transcription; HES1 knockdown partially abolishes MYEOV oncogenic effects in pancreatic cancer. Co-immunoprecipitation of MYEOV and SOX9; ChIP of SOX9 at HES1 enhancer; HES1 reporter assays; HES1 knockdown rescue experiments Oncogene Medium 32879444
2023 HES1 directly binds the IGF2BP2 promoter and promotes IGF2BP2 expression; IGF2BP2 then recognizes and binds the m6A site in GLUT1 mRNA, enhancing its stability and promoting aerobic glycolysis in colorectal cancer cells. ChIP-PCR of HES1 at IGF2BP2 promoter; dual-luciferase reporter assay; HES1/IGF2BP2 knockdown; GLUT1 mRNA stability measurement; m6A site analysis Cell death discovery Medium 37957183

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Control of endodermal endocrine development by Hes-1. Nature genetics 930 10615124
1999 Hes1 and Hes5 as notch effectors in mammalian neuronal differentiation. The EMBO journal 699 10205173
2003 Oscillatory expression of Hes1, p53, and NF-kappaB driven by transcriptional time delays. Current biology : CB 403 12932324
1998 Delta-1 activation of notch-1 signaling results in HES-1 transactivation. Molecular and cellular biology 283 9819428
2000 The bHLH gene Hes6, an inhibitor of Hes1, promotes neuronal differentiation. Development (Cambridge, England) 216 10851137
2005 Hes1 directly controls cell proliferation through the transcriptional repression of p27Kip1. Molecular and cellular biology 183 15870295
2006 Persistent and high levels of Hes1 expression regulate boundary formation in the developing central nervous system. Development (Cambridge, England) 177 16728479
2000 A role for pref-1 and HES-1 in thymocyte development. Journal of immunology (Baltimore, Md. : 1950) 164 10605019
2007 Id sustains Hes1 expression to inhibit precocious neurogenesis by releasing negative autoregulation of Hes1. Developmental cell 158 17681138
2015 Hes1: a key role in stemness, metastasis and multidrug resistance. Cancer biology & therapy 151 25781910
2015 Wnt and Notch signaling pathway involved in wound healing by targeting c-Myc and Hes1 separately. Stem cell research & therapy 135 26076648
2007 Integrative genomic analyses on HES/HEY family: Notch-independent HES1, HES3 transcription in undifferentiated ES cells, and Notch-dependent HES1, HES5, HEY1, HEY2, HEYL transcription in fetal tissues, adult tissues, or cancer. International journal of oncology 134 17611704
2019 High Hes1 expression and resultant Ascl1 suppression regulate quiescent vs. active neural stem cells in the adult mouse brain. Genes & development 132 30862661
2006 p57 and Hes1 coordinate cell cycle exit with self-renewal of pancreatic progenitors. Developmental biology 130 16899237
2004 Dual roles for the Notch target gene Hes-1 in the differentiation of 3T3-L1 preadipocytes. Molecular and cellular biology 129 15060169
2000 The bHLH gene Hes1 regulates differentiation of multiple cell types. Molecules and cells 128 10774739
2007 Ultradian oscillations of Stat, Smad, and Hes1 expression in response to serum. Proceedings of the National Academy of Sciences of the United States of America 105 17592117
2006 HES1 inhibits cycling of hematopoietic progenitor cells via DNA binding. Stem cells (Dayton, Ohio) 98 16513761
2005 Multiple requirements for Hes 1 during early eye formation. Developmental biology 93 16038893
2008 Expression and function of the Delta-1/Notch-2/Hes-1 pathway during experimental acute kidney injury. Kidney international 90 18418349
2014 Hes1 is involved in the self-renewal and tumourigenicity of stem-like cancer cells in colon cancer. Scientific reports 87 24492635
2006 Notch-independent regulation of Hes-1 expression by c-Jun N-terminal kinase signaling in human endothelial cells. Laboratory investigation; a journal of technical methods and pathology 82 16732296
2009 Hijacking HES1: how tumors co-opt the anti-differentiation strategies of quiescent cells. Trends in molecular medicine 78 20022559
2016 The transcriptional repressor Hes1 attenuates inflammation by regulating transcription elongation. Nature immunology 76 27322654
2010 Hes1 regulates embryonic stem cell differentiation by suppressing Notch signaling. Genes to cells : devoted to molecular & cellular mechanisms 73 20545770
2009 The notch target gene HES1 regulates cell cycle inhibitor expression in the developing pituitary. Endocrinology 73 19541765
2012 The putative tumor suppressor miR-524-5p directly targets Jagged-1 and Hes-1 in glioma. Carcinogenesis 71 22871495
2004 Expression of Hairy/Enhancer of Split genes, Hes1 and Hes5, during murine nephron morphogenesis. Gene expression patterns : GEP 71 15465493
2006 Hes1 is required for pituitary growth and melanotrope specification. Developmental biology 70 17367776
2016 HES1 in immunity and cancer. Cytokine & growth factor reviews 69 27066918
2019 Oscillations of MyoD and Hes1 proteins regulate the maintenance of activated muscle stem cells. Genes & development 66 30862660
2016 A CREB-Sirt1-Hes1 Circuitry Mediates Neural Stem Cell Response to Glucose Availability. Cell reports 61 26804914
2016 Hes1: the maestro in neurogenesis. Cellular and molecular life sciences : CMLS 58 27233500
2020 Oscillatory expression of Hes1 regulates cell proliferation and neuronal differentiation in the embryonic brain. Development (Cambridge, England) 57 32094111
1999 Regulation of hippocampal neuronal differentiation by the basic helix-loop-helix transcription factors HES-1 and MASH-1. Journal of neuroscience research 55 10336252
2015 Activation of OR1A1 suppresses PPAR-γ expression by inducing HES-1 in cultured hepatocytes. The international journal of biochemistry & cell biology 54 25817041
2012 GATA-1 utilizes Ikaros and polycomb repressive complex 2 to suppress Hes1 and to promote erythropoiesis. Molecular and cellular biology 54 22778136
2011 Notch/HES1-mediated PARP1 activation: a cell type-specific mechanism for tumor suppression. Blood 54 21224467
2004 HES-1, a novel target gene for the aryl hydrocarbon receptor. Molecular pharmacology 54 14722248
2004 Roles of the bHLH gene Hes1 in retinal morphogenesis. Brain research 53 15033430
2019 DNA-methylation-mediated silencing of miR-7-5p promotes gastric cancer stem cell invasion via increasing Smo and Hes1. Journal of cellular physiology 52 31517391
2015 Deubiquitinating enzymes regulate Hes1 stability and neuronal differentiation. The FEBS journal 52 25846153
2015 miR-381 Regulates Neural Stem Cell Proliferation and Differentiation via Regulating Hes1 Expression. PloS one 51 26431046
2004 HES-1 inhibits 17beta-estradiol and heregulin-beta1-mediated upregulation of E2F-1. Oncogene 51 15467735
2010 HES1 (hairy and enhancer of split 1) is a determinant of bone mass. The Journal of biological chemistry 50 21084301
2012 The micro-RNA 199b-5p regulatory circuit involves Hes1, CD15, and epigenetic modifications in medulloblastoma. Neuro-oncology 48 22411914
2015 Hes1 promotes cell proliferation and migration by activating Bmi-1 and PTEN/Akt/GSK3β pathway in human colon cancer. Oncotarget 46 26452029
2004 The Notch signaling cascade in neuroblastoma: role of the basic helix-loop-helix proteins HASH-1 and HES-1. Cancer letters 46 15013216
2016 Tigecycline Inhibits Glioma Growth by Regulating miRNA-199b-5p-HES1-AKT Pathway. Molecular cancer therapeutics 42 26823491
2021 HES1 and HES4 have non-redundant roles downstream of Notch during early human T-cell development. Haematologica 39 31919081
2015 Therapeutic targeting of HES1 transcriptional programs in T-ALL. Blood 39 25784680
2020 Hes1 deficiency causes hematopoietic stem cell exhaustion. Stem cells (Dayton, Ohio) 36 32129527
2019 Hes1 regulates anagen initiation and hair follicle regeneration through modulation of hedgehog signaling. Stem cells (Dayton, Ohio) 36 31721388
2014 Hes1 suppresses acute myeloid leukemia development through FLT3 repression. Leukemia 36 25234168
2018 Epithelial Hes1 maintains gut homeostasis by preventing microbial dysbiosis. Mucosal immunology 35 29297498
2023 HES1 promotes aerobic glycolysis and cancer progression of colorectal cancer via IGF2BP2-mediated GLUT1 m6A modification. Cell death discovery 32 37957183
2020 MYEOV increases HES1 expression and promotes pancreatic cancer progression by enhancing SOX9 transactivity. Oncogene 32 32879444
1994 Genomic cloning and chromosomal localization of HRY, the human homolog to the Drosophila segmentation gene, hairy. Genomics 32 8020957
2023 Differential cell-cycle control by oscillatory versus sustained Hes1 expression via p21. Cell reports 31 37200191
2020 Simultaneous Requirements for Hes1 in Retinal Neurogenesis and Optic Cup-Stalk Boundary Maintenance. The Journal of neuroscience : the official journal of the Society for Neuroscience 30 31949107
2019 Hes1 plays an essential role in Kras-driven pancreatic tumorigenesis. Oncogene 30 30705405
2013 The role of dimerisation and nuclear transport in the Hes1 gene regulatory network. Bulletin of mathematical biology 29 23686434
2016 Hes1 Controls Exocrine Cell Plasticity and Restricts Development of Pancreatic Ductal Adenocarcinoma in a Mouse Model. The American journal of pathology 28 27639167
2008 HES1 regulates 5-HT1A receptor gene transcription at a functional polymorphism: essential role in developmental expression. Molecular and cellular neurosciences 28 18499474
2012 miR-1-mediated induction of cardiogenesis in mesenchymal stem cells via downregulation of Hes-1. BioMed research international 27 23509692
2024 Curcumin pretreatment attenuates myocardial ischemia/reperfusion injury by inhibiting ferroptosis, autophagy and apoptosis via HES1. International journal of molecular medicine 26 39364745
2022 Targeting the transcription factor HES1 by L-menthol restores protein phosphatase 6 in keratinocytes in models of psoriasis. Nature communications 26 36535970
2018 microRNA-203 Modulates Wound Healing and Scar Formation via Suppressing Hes1 Expression in Epidermal Stem Cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 26 30261495
2009 Hes-6, an inhibitor of Hes-1, is regulated by 17beta-estradiol and promotes breast cancer cell proliferation. Breast cancer research : BCR 26 19891787
2021 HES1 promotes breast cancer stem cells by elevating Slug in triple-negative breast cancer. International journal of biological sciences 25 33390847
2014 Control of hair cell development by molecular pathways involving Atoh1, Hes1 and Hes5. Gene 25 25550047
2011 Notch signalling is off and is uncoupled from HES1 expression in Ewing's sarcoma. The Journal of pathology 25 21984123
2014 Regulation of a Notch3-Hes1 pathway and protective effect by a tocopherol-omega alkanol chain derivative in muscle atrophy. The Journal of pharmacology and experimental therapeutics 24 25326132
2012 The expression of NOTCH2, HES1 and SOX9 during mouse retinal development. Gene expression patterns : GEP 24 23277114
2021 Hes1 overexpression leads to expansion of embryonic neural stem cell pool and stem cell reservoir in the postnatal brain. Development (Cambridge, England) 23 33531431
2012 PDX-1/Hes-1 interactions determine cholangiocyte proliferative response to injury in rodents: possible implications for sclerosing cholangitis. Journal of hepatology 23 23207146
2021 The NOTCH-HES-1 axis is involved in promoting Th22 cell differentiation. Cellular & molecular biology letters 22 33622250
2021 Rutin Mediated Apoptotic Cell Death in Caski Cervical Cancer Cells via Notch-1 and Hes-1 Downregulation. Life (Basel, Switzerland) 22 34440505
2013 The jagged-2/notch-1/hes-1 pathway is involved in intestinal epithelium regeneration after intestinal ischemia-reperfusion injury. PloS one 22 24098462
2021 HES1 protein oscillations are necessary for neural stem cells to exit from quiescence. iScience 21 34703994
2022 Medial prefrontal cortex Notch1 signalling mediates methamphetamine-induced psychosis via Hes1-dependent suppression of GABAB1 receptor expression. Molecular psychiatry 20 35732696
2019 Hes1 attenuates type I IFN responses via VEGF-C and WDFY1. The Journal of experimental medicine 20 31015298
2017 miR-1297 regulates neural stem cell differentiation and viability through controlling Hes1 expression. Cell proliferation 20 28464358
2021 Melatonin attenuates aortic oxidative stress injury and apoptosis in STZ-diabetes rats by Notch1/Hes1 pathway. The Journal of steroid biochemistry and molecular biology 19 34224859
2017 Inhibition of Notch1/Hes1 signaling pathway improves radiosensitivity of colorectal cancer cells. European journal of pharmacology 19 29126793
2010 Hes1/Hes5 gene inhibits differentiation via down-regulating Hash1 and promotes proliferation in cervical carcinoma cells. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 19 21495212
2008 TGF-alpha induces upregulation and nuclear translocation of Hes1 in glioma cell. Cell biochemistry and function 19 18636433
2019 SP promotes cell proliferation in esophageal squamous cell carcinoma through the NK1R/Hes1 axis. Biochemical and biophysical research communications 17 31109645
2017 Separate and coincident expression of Hes1 and Hes5 in the developing mouse eye. Developmental dynamics : an official publication of the American Association of Anatomists 17 28675662
2022 RNF144B stimulates the proliferation and inhibits the apoptosis of human spermatogonial stem cells via the FCER2/NOTCH2/HES1 pathway and its abnormality is associated with azoospermia. Journal of cellular physiology 16 35699595
2022 HES1 promoter activation dynamics reveal the plasticity, stemness and heterogeneity in neuroblastoma cancer stem cells. Journal of cell science 16 36321463
2020 Hes1 Is Essential in Proliferating Ductal Cell-Mediated Development of Intrahepatic Cholangiocarcinoma. Cancer research 16 33067264
2005 Overexpression of HES-1 is not sufficient to impose T-cell differentiation on human hematopoietic stem cells. Blood 16 16322473
1998 Genetic elements regulating HES-1 induction in Wnt-1-transformed PC12 cells. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 15 9790494
2021 ETV4 transcriptionally activates HES1 and promotes Stat3 phosphorylation to promote malignant behaviors of colon adenocarcinoma. Cell biology international 14 34270850
2021 RASSF1A disrupts the NOTCH signaling axis via SNURF/RNF4-mediated ubiquitination of HES1. EMBO reports 14 34897944
2019 Synchronization of Hes1 oscillations coordinates and refines condensation formation and patterning of the avian limb skeleton. Mechanisms of development 14 30867133
2019 Somatostatin stimulates colonic MUC2 expression through SSTR5-Notch-Hes1 signaling pathway. Biochemical and biophysical research communications 14 31733832
2018 Hairy and enhancer of split 1 (HES1) protects cells from endoplasmic reticulum stress-induced apoptosis through repression of . The Journal of biological chemistry 14 29491143
2013 Jagged-1-HES-1 signaling inhibits the differentiation of TH17 cells via ROR gammat. Journal of biological regulators and homeostatic agents 14 23489689

Missed literature

Know a paper Affinage missed for HES1? Flag it for the maintainers and the community.

No submissions yet.