Affinage

HES6

Transcription cofactor HES-6 · UniProt Q96HZ4

Length
224 aa
Mass
24.1 kDa
Annotated
2026-06-10
43 papers in source corpus 22 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HES6 is a bHLH transcriptional co-factor that promotes neuronal and myogenic differentiation by antagonizing the anti-neurogenic/anti-myogenic activity of HES1 and related HES/Hairy repressors, acting predominantly through protein–protein interactions rather than its own DNA binding (PMID:10851137, PMID:17065448, PMID:22114720). HES6 expression is driven by proneural and myogenic transcription factors—induced by neurogenins independently of Notch (PMID:10976052) and a direct target of MyoD/Myf5 (PMID:21501606)—placing it in a positive-feedback differentiation circuit. Mechanistically, HES6 suppresses HES1-mediated repression both by disrupting the HES1–Groucho/TLE co-repressor interaction and by promoting proteolytic degradation of HES1, with both activities depending on its C-terminal WRPW motif and a CK2 phosphorylation site (Ser183) (PMID:12972610). The WRPW motif mediates direct binding to Groucho/TLE proteins to relieve their repression of proneural and myogenic targets (PMID:11551980, PMID:17950722), and itself functions as a proteasomal degradation signal (PMID:15896295). HES6 preferentially homodimerizes, and a homodimer-dependent MAPK phosphorylation of a C-terminal SPXXSP motif governs its inhibition of astrocyte differentiation, a function separable from HES1 suppression (PMID:17868320); sumoylation at Lys27/30 controls its stability and ~2-hour oscillatory expression (PMID:26435136). In oscillatory networks such as the zebrafish segmentation clock, HES6 acts as a dimerization hub whose sequestration by partner Her proteins reshapes network topology and DNA-binding output (PMID:22278920). In disease and lineage contexts, HES6 enhances androgen receptor transcriptional output toward E2F1-enriched networks to drive castration-resistant prostate cancer (PMID:24737870), and physically interacts with GATA1 to regulate erythroid and broader hematopoietic differentiation downstream of EPO signaling (PMID:36929421, PMID:38572564).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 2000 High

    Established that HES6 is not a conventional DNA-binding repressor but a modulator that derepresses proneural activity by counteracting HES1, defining its core regulatory logic.

    Evidence Transcriptional reporter assays, retroviral misexpression in developing retina, and loop-region mutagenesis

    PMID:10851137

    Open questions at the time
    • Did not resolve whether antagonism is via sequestration, co-repressor displacement, or degradation
    • In vivo developmental requirement not tested by loss-of-function
  2. 2000 High

    Placed HES6 in a positive-feedback loop downstream of proneural bHLH factors and independent of Notch, explaining how it reinforces rather than opposes neurogenesis.

    Evidence Xenopus ectopic expression, in situ hybridization, and epistasis analysis

    PMID:10976052

    Open questions at the time
    • Direct transcriptional regulation of Hes6 by neurogenins not shown at promoter level
    • Endogenous requirement not addressed
  3. 2001 High

    Identified the WRPW-dependent interaction with Groucho/TLE1 and extended HES6 function to myogenesis via repression of the myogenic inhibitor MyoR.

    Evidence Yeast two-hybrid, mammalian Co-IP, GAL4-tethering, reporter assays, and dominant-negative ΔWRPW in myoblasts

    PMID:11551980

    Open questions at the time
    • Whether TLE binding is required for HES1 antagonism not yet distinguished from N-box co-repression
    • Direct vs indirect MyoR repression unresolved
  4. 2002 High

    Demonstrated HES6 can directly bind the ESE E-box motif yet showed protein-protein interactions, not DNA binding, drive its myogenic phenotype, separating its two potential modes of action.

    Evidence EMSA, reporter assays, C2C12 overexpression, and Xenopus microinjection with domain mutants

    PMID:11959828

    Open questions at the time
    • Physiological relevance of direct ESE binding in mammals unclear
    • Effect on terminal differentiation context-dependent
  5. 2003 High

    Resolved the dual mechanism of HES1 antagonism—co-repressor displacement and proteolytic degradation—and tied both to the WRPW motif and CK2 phosphorylation at Ser183.

    Evidence Co-IP, reporter assays in cortical progenitors, Ser183 mutagenesis, and protein-stability Western blots

    PMID:12972610

    Open questions at the time
    • Identity of the ubiquitin ligase/proteasomal machinery for HES1 not defined
    • Direct CK2 phosphorylation of HES6 not demonstrated biochemically
  6. 2005 Medium

    Showed the WRPW motif doubles as a proteasomal degradation signal, explaining how HES6 stability is intrinsically regulated.

    Evidence Proteasome-inhibition Western blots with WRPW-deletion and WRPW-GFP/GAL4 fusion constructs

    PMID:15896295

    Open questions at the time
    • Single lab; degron mechanism and responsible E3 ligase not identified
    • Relationship to WRPW co-repressor binding not dissected
  7. 2005 Medium

    Embedded HES6 in a cyclic Notch-effector circuit by showing reciprocal repression between hes6 and hes5 during neurogenesis.

    Evidence In situ hybridization and gain-of-function electroporation in chick neural tube with epistasis

    PMID:15893982

    Open questions at the time
    • Single lab; direct vs indirect repression not established
    • Loss-of-function not tested
  8. 2006 High

    Defined an anti-astrogenic role for endogenous HES6 in cortical progenitors and mapped it to nuclear localization plus the LNHLL and WRPW motifs, independent of basic-arm DNA binding.

    Evidence siRNA knockdown, retroviral overexpression, domain mutagenesis, and GFAP immunostaining in cortical progenitors

    PMID:17065448

    Open questions at the time
    • Molecular target mediating astrocyte suppression not identified at this stage
    • How motifs cooperate mechanistically unresolved
  9. 2007 High

    Showed HES6 preferentially homodimerizes and that homodimer-dependent MAPK phosphorylation of a SPXXSP motif specifically controls astrocyte inhibition, separating this output from HES1 suppression.

    Evidence Co-IP dimerization assays, N-terminal patch and SPXXSP mutagenesis, reporter and differentiation assays in cortical progenitors

    PMID:17868320

    Open questions at the time
    • Direct MAPK phosphorylation site usage not confirmed in vivo
    • Downstream effectors of homodimer signaling unknown
  10. 2007 High

    Demonstrated that HES6 is required for FGF-mediated myogenic induction by binding Groucho proteins to relieve their repression of XmyoD.

    Evidence Morpholino knockdown, Co-IP with Xgrg2/4, and domain-mutant rescue in Xenopus

    PMID:17950722

    Open questions at the time
    • Whether HES6 acts directly at the XmyoD locus not shown
    • Single-system (Xenopus) finding
  11. 2008 Medium

    Connected HES6 to cell-cycle control by identifying a CBP interaction at PML nuclear bodies that induces p21 via p53 acetylation.

    Evidence Co-IP with domain mapping, immunofluorescence, reporter assays, and p53 acetylation/p21 induction assays

    PMID:18160400

    Open questions at the time
    • Single lab; not independently replicated
    • Relevance to neuronal/myogenic differentiation contexts unclear
  12. 2010 Medium

    Distinguished two mechanistically distinct HES6 subgroups—one acting by protein sequestration of HES proteins, the other by direct DNA-binding repression of Hes5/Delta.

    Evidence Ectopic expression in chick neural tube with reporter assays and DNA-binding-mutant dissection

    PMID:21151987

    Open questions at the time
    • Single lab; mammalian relevance of the two-subgroup model not established
    • Loss-of-function not assessed
  13. 2011 Medium

    Confirmed in vivo that HES6 is required for neural differentiation via WRPW-dependent, DNA-binding-independent dual mechanisms.

    Evidence Morpholino knockdown in Xenopus with DNA-binding and WRPW mutant rescue

    PMID:22114720

    Open questions at the time
    • Single lab; specific Hairy/Groucho partners in this context not fully enumerated
  14. 2011 High

    Identified HES6 as a direct MyoD/Myf5 target controlling cytoskeletal dynamics and myoblast fusion rather than cell-cycle exit, refining its myogenic role.

    Evidence ChIP, siRNA knockdown with rescue, nuclear-localization imaging, F-actin staining, and motility/fusion assays in C2C12

    PMID:21501606

    Open questions at the time
    • Mechanism linking HES6 to F-actin organization not defined here
    • Transcriptional targets in fusion not identified
  15. 2012 High

    Established HES6 as a dimerization hub in the zebrafish segmentation clock whose sequestration tunes oscillatory network topology and DNA-binding specificity.

    Evidence In vitro dimerization assays, in vivo zebrafish genetics, EMSA, and computational network analysis

    PMID:22278920

    Open questions at the time
    • Quantitative impact on oscillation period not fully resolved
    • Mammalian equivalent network not mapped
  16. 2012 Medium

    Linked HES6 to oncogenic motility in rhabdomyosarcoma through transcriptional upregulation of the actin regulator TAGLN.

    Evidence siRNA with rescue, expression microarray, and TAGLN epistasis with motility assays

    PMID:22982728

    Open questions at the time
    • Single lab; direct vs indirect TAGLN regulation unclear
    • Whether bHLH partners mediate this not addressed
  17. 2009 Medium

    Identified HES6 as an estrogen-inducible driver of breast cancer proliferation acting through induction of E2F1.

    Evidence Lentiviral overexpression, siRNA knockdown, xenografts, and expression analysis of E2F1/hASH-1

    PMID:19891787

    Open questions at the time
    • Single lab; direct transcriptional mechanism for E2F1 induction not defined
    • Connection to bHLH co-factor activity unclear
  18. 2014 High

    Showed HES6 reprograms androgen receptor transcriptional output toward E2F1 networks to drive ligand-independent, castration-resistant prostate cancer growth.

    Evidence AR/HES6 ChIP-seq, gene expression profiling, overexpression, and xenograft assays

    PMID:24737870

    Open questions at the time
    • Direct physical interaction between HES6 and AR not established
    • Mechanism of AR genomic redistribution not detailed
  19. 2015 Medium

    Demonstrated that sumoylation at Lys27/30 destabilizes HES6, drives its ultradian oscillation, and derepresses HES1, linking post-translational modification to dynamic output.

    Evidence SUMO/ubiquitin Co-IP, stability Westerns, K27R/K30R and SUSP1 mutagenesis, and live-cell GFP-HES6 oscillation imaging

    PMID:26435136

    Open questions at the time
    • Single lab; responsible SUMO ligase not identified
    • Coupling between sumoylation and WRPW degron unresolved
  20. 2023 High

    Defined a direct HES6–GATA1 interaction that modulates GATA1–FOG1 binding and operates within an EPO-driven HES6/GATA1/STAT1 feedback loop controlling erythropoiesis.

    Evidence Reciprocal Co-IP, ChIP-seq, RNA-seq, siRNA knockdown, and an in vivo polycythemia vera mouse model

    PMID:36929421

    Open questions at the time
    • Structural basis of HES6-GATA1 interaction unknown
    • Relationship to bHLH/WRPW functions not connected
  21. 2024 High

    Broadened HES6's hematopoietic role beyond erythropoiesis, showing it is required for multilineage differentiation and reconstitution and for cell-cycle progression during erythropoiesis.

    Evidence shRNA knockdown in cord-blood HSPCs, differentiation and CFU assays, competitive transplantation, and single-cell/bulk RNA-seq

    PMID:38572564

    Open questions at the time
    • Molecular partners in non-erythroid lineages not identified
    • Mechanism of cell-cycle perturbation undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the distinct molecular activities of HES6—co-repressor displacement, HES protein sequestration, direct DNA binding, dimerization-hub behavior, and lineage-specific transcription-factor partnerships—are selected in a given cell type, and how its post-translational modifications integrate to set this choice, remains unresolved.
  • No unified structural/biochemical model of HES6 partner selection
  • E3 ligases and kinases acting on HES6 not fully identified
  • Direct AR and proneural-locus binding events incompletely mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0098772 molecular function regulator activity 4 GO:0003677 DNA binding 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005634 nucleus 2 GO:0005654 nucleoplasm 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1643685 Disease 3
Partners
CBPGATA1GRG2GRG4HES1RELATLE1

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 HES6 alone does not bind DNA but suppresses HES1-mediated transcriptional repression; it also suppresses HES1 from inhibiting MASH1-E47 heterodimer activity, thereby enabling MASH1/E47 to upregulate transcription in the presence of HES1. Loop-region swap mutagenesis showed the loop determines HES1- vs HES6-specific functions. Transcriptional reporter assays, retroviral misexpression in developing retina, site-directed mutagenesis of loop region Development High 10851137
2000 HES6 expression is induced by proneural bHLH proteins (neurogenins) but not by the Notch pathway; ectopic HES6 expression in Xenopus embryos promotes neurogenesis, placing HES6 in a positive-feedback loop with proneural factors downstream of neurogenins. Xenopus ectopic expression, in situ hybridization, epistasis analysis Development High 10976052
2003 HES6 antagonizes HES1 by two mechanisms: (1) it inhibits the interaction of HES1 with its transcriptional co-repressor GRO/TLE, and (2) it promotes proteolytic degradation of HES1. Both effects require the WRPW motif and are reduced when the conserved CK2 phosphorylation site Ser183 is mutated. Co-immunoprecipitation, reporter assays in cortical neural progenitors, site-directed mutagenesis (Ser183), Western blot (protein stability) Molecular and cellular biology High 12972610
2001 HES6 interacts with the transcriptional co-repressor TLE1 (Groucho) via its WRPW C-terminal motif, represses transcription from N-box-containing templates, and cooperates with HES1 for maximal N-box repression. HES6 expression induces myotube differentiation by repressing MyoR, a repressor of myogenesis. Yeast two-hybrid and mammalian Co-IP (HES6-TLE1 interaction), reporter assays, GAL4-tethering assay, dominant-negative (ΔWRPW) HES6, myosin heavy chain and MyoR expression analysis The Journal of cell biology High 11551980
2002 HES6 binds DNA at the Enhancer of Split E-box (ESE) motif (preferred binding site of Drosophila EoS proteins) and represses ESE-box reporter transcription. Overexpression in C2C12 myoblasts impairs terminal differentiation (decreased p21 induction, increased re-entry into cell cycle). Protein-protein interactions rather than DNA binding are required for the myogenic phenotype in Xenopus. Electrophoretic mobility shift assay (EMSA), reporter assay, C2C12 overexpression, Xenopus microinjection, HES6 domain mutant analysis Development High 11959828
2005 The WRPW motif of HES6 acts as a proteasomal degradation signal: WRPW-deletion mutant protein is substantially stabilized due to resistance to proteasomal degradation. Fusion of WRPW to GFP or GAL4-DBD significantly destabilizes these heterologous proteins. Western blot (protein stability after proteasome inhibition), WRPW-deletion and fusion constructs in cell lines Biochemical and biophysical research communications Medium 15896295
2005 In chick, hes6-2 represses transcription of hes5 genes (downstream Notch effectors), forming a negative regulatory circuit: hes5 can repress hes6, and hes6 can repress hes5, providing cyclic regulation of Notch signaling during neurogenesis. In situ hybridization, gain-of-function electroporation in chick neural tube, epistasis analysis Developmental biology Medium 15893982
2006 Knockdown of endogenous HES6 in cortical progenitors causes supernumerary cells to adopt an astrocytic fate (GFAP+), while HES6 overexpression inhibits astrocyte differentiation. The anti-astrogenic activity requires nuclear localization and the LNHLL and WRPW peptide motifs but is independent of DNA binding via the basic arm of the bHLH domain. siRNA knockdown, retroviral overexpression, domain deletion/mutation analysis, immunostaining (GFAP), cortical progenitor cultures The Journal of neuroscience High 17065448
2007 HES6 preferentially forms homodimers; a conserved N-terminal patch of negatively charged residues antagonizes heterodimerization with HES1. Mutation of this motif enhances HES1 heterodimerization and Hes1 suppression but paradoxically decreases anti-astrogenic activity. A C-terminal SPXXSP motif is phosphorylated by the MAPK pathway and its mutation disrupts anti-astrogenic activity without affecting HES1 suppression, indicating that HES6 homodimer-dependent MAPK phosphorylation governs astrocyte inhibition. Co-IP (dimerization), site-directed mutagenesis (N-terminal patch, SPXXSP), reporter assays, cortical progenitor differentiation assays Journal of neurochemistry High 17868320
2007 In Xenopus, HES6 is required for FGF-mediated induction of XmyoD expression; the WRPW domain (Groucho-binding) is essential for this activity. HES6 binds Groucho family members Xgrg2 and Xgrg4, relieving their repression of XmyoD expression. Morpholino knockdown in Xenopus, co-immunoprecipitation (HES6-Xgrg2/4 interaction), domain mutant rescue experiments Developmental biology High 17950722
2007 HES6 localizes to promyelocytic leukemia nuclear bodies (PML-NB) and directly interacts with CREB-binding protein (CBP) via its basic domain. This HES6-CBP complex induces p21 CDK inhibitor expression through chromatin remodeling and p53 acetylation, inhibiting cell proliferation. Co-IP (HES6-CBP), immunofluorescence (PML-NB localization), reporter assays, p53 acetylation (Western blot), p21 induction assays The Journal of biological chemistry Medium 18160400
2011 In Xenopus, HES6 depletion by morpholino antisense prevents neural differentiation. Rescue requires WRPW motif (Groucho/TLE binding) but not DNA binding, and HES6 acts through at least two mechanisms: inhibiting anti-neurogenic Hairy proteins and interacting with Groucho/TLE family proteins. Morpholino antisense knockdown in Xenopus, domain mutant rescue (DNA-binding mutant, WRPW mutant) PloS one Medium 22114720
2011 HES6 is a direct transcriptional target of MyoD and Myf5 in C2C12 myoblasts. During differentiation, HES6 protein relocates to the nucleus. HES6 siRNA knockdown does not affect cell cycle exit or myosin heavy chain induction but disrupts F-actin filament formation, reduces cell motility, and impairs myoblast fusion. ChIP (MyoD/Myf5 binding to Hes6 promoter), siRNA knockdown, immunofluorescence (nuclear localization), F-actin staining, cell motility assays, siRNA-resistant rescue construct Experimental cell research High 21501606
2012 In the zebrafish segmentation clock, HES6 serves as a dimerization hub: Her1, Her12, Her15, and Her7 all dimerize with HES6. Her7 sequestration of HES6 reduces HES6 availability for other heterodimers, thereby modulating network topology. Dimers that include HES6 have distinct DNA-binding preferences for cis-regulatory sequences. In vitro dimerization assays, in vivo genetic experiments (zebrafish), electrophoretic mobility shift assay (DNA-binding specificity), computational network analysis Development High 22278920
2012 HES6 overexpression in rhabdomyosarcoma (ARMSp) cells enhances proliferation and cell motility; knockdown reduces both. HES6 regulates motility via upregulation of Transgelin (TAGLN), an actin cytoskeleton regulator; TAGLN knockdown phenocopies HES6 knockdown motility defect and TAGLN overexpression rescues HES6-knockdown motility loss. siRNA knockdown, mouse Hes6 rescue (siRNA-resistant), expression microarray, TAGLN knockdown/overexpression, cell motility assays Experimental cell research Medium 22982728
2014 HES6 enhances androgen receptor (AR) transcriptional activity in prostate cancer cells and redirects AR preferentially to a regulatory network enriched for E2F1 transcription factor targets, driving castration-resistant tumor growth in the absence of ligand. ChIP-seq (AR and HES6 genome-wide binding), gene expression profiling, lentiviral overexpression, xenograft tumor growth assays EMBO molecular medicine High 24737870
2015 SUMO modification of HES6 occurs at lysines 27 and 30. Sumoylation destabilizes HES6 protein (by promoting ubiquitination and proteasomal degradation) and is required for its ~2-hour oscillatory expression rhythm. Sumoylation of HES6 also derepresses HES1-induced transcriptional repression. Co-transfection and immunoprecipitation (sumo/ubiquitin), Western blot (protein stability), site-directed mutagenesis (K27R/K30R and SUMO protease SUSP1), live-cell imaging of GFP-HES6 oscillations Endocrinology and metabolism Medium 26435136
2009 HES6 overexpression in T47D breast cancer cells stimulates proliferation in vitro and tumor growth in xenografts; it induces E2F1 expression, and HES6 siRNA knockdown downregulates E2F1. Estrogen (17β-estradiol) treatment induces HES6 expression in MCF-7 cells, which subsequently induces hASH-1 and E2F1. Lentiviral stable overexpression, siRNA knockdown, xenograft tumor growth assay, gene expression analysis (E2F1, hASH-1) Breast cancer research Medium 19891787
2010 Chick HES6-1 promotes neurogenesis by sequestering other HES proteins and inhibiting their transcriptional repressor activity (protein-protein mechanism), while HES6-2 promotes neurogenesis by directly binding DNA and repressing transcription of Hes5 and Delta genes—indicating two mechanistically distinct subgroups. Ectopic expression in chick neural tube, reporter assays, domain mutant analysis (DNA-binding mutant of HES6-2) PloS one Medium 21151987
2013 HES6 physically and functionally interacts with RelA-containing NF-κB complexes in cortical progenitor cells, antagonizing NF-κB activity. NF-κB promotes progenitor maintenance and inhibits neuronal differentiation, while HES6 counters this to promote neurogenesis; the two factors exert mutual inhibitory effects. Co-immunoprecipitation (HES6-RelA), reporter assays, NF-κB blockade/activation experiments in cortical progenitors, in vivo mouse telencephalon analysis Molecular and cellular biology Medium 23689134
2023 HES6 physically interacts with GATA1 and modulates GATA1's interaction with FOG1 during human erythropoiesis. HES6 knockdown decreases GATA1 expression and impairs erythroid differentiation. ChIP-seq and RNA-seq identified co-regulated erythroid genes. A positive feedback loop comprising HES6, GATA1, and STAT1 is activated by erythropoietin (EPO) signaling. Co-immunoprecipitation (HES6-GATA1, GATA1-FOG1), ChIP-seq, RNA-seq, siRNA knockdown, in vivo mouse polycythemia vera model Nucleic acids research High 36929421
2024 HES6 knockdown in human cord-blood hematopoietic precursors reduces differentiation into erythrocytes, megakaryocytes, plasmacytoid dendritic cells, B cells, and T cells, impairs colony-forming ability in vitro, and reduces hematopoietic reconstitution in vivo. HES6 loss perturbs cell cycle progression during erythroid differentiation. shRNA knockdown in cord blood HSPCs, in vitro differentiation assays, colony-forming unit assay, competitive transplantation in vivo, single-cell and bulk RNA-seq Haematologica High 38572564
2024 STAT3 mutations suppress HES6 expression in bronchial epithelial cells, impairing ciliogenesis and mucociliary transport. A γ-secretase inhibitor increases HES6 expression and rescues ciliogenesis in STAT3 R382W mutant cells, placing HES6 downstream of STAT3 in airway epithelial ciliogenesis. Lentiviral STAT3 mutant expression, CRISPR/Cas9 STAT3 knockout, transcriptomics, γ-secretase inhibitor rescue, ciliogenesis and mucociliary transport functional assays bioRxiv (preprint)preprint Medium

Source papers

Stage 0 corpus · 43 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 The bHLH gene Hes6, an inhibitor of Hes1, promotes neuronal differentiation. Development (Cambridge, England) 216 10851137
2000 Hes6 acts in a positive feedback loop with the neurogenins to promote neuronal differentiation. Development (Cambridge, England) 119 10976052
2003 Hes6 promotes cortical neurogenesis and inhibits Hes1 transcription repression activity by multiple mechanisms. Molecular and cellular biology 103 12972610
2005 A novel hes5/hes6 circuitry of negative regulation controls Notch activity during neurogenesis. Developmental biology 94 15893982
2021 Single-cell RNA sequencing reveals intratumoral heterogeneity in primary uveal melanomas and identifies HES6 as a driver of the metastatic disease. Cell death and differentiation 76 33462406
2014 HES6 drives a critical AR transcriptional programme to induce castration-resistant prostate cancer through activation of an E2F1-mediated cell cycle network. EMBO molecular medicine 71 24737870
2002 Hes6 regulates myogenic differentiation. Development (Cambridge, England) 59 11959828
2006 Hes6 inhibits astrocyte differentiation and promotes neurogenesis through different mechanisms. The Journal of neuroscience : the official journal of the Society for Neuroscience 57 17065448
2001 HES6 acts as a transcriptional repressor in myoblasts and can induce the myogenic differentiation program. The Journal of cell biology 53 11551980
2012 The Her7 node modulates the network topology of the zebrafish segmentation clock via sequestration of the Hes6 hub. Development (Cambridge, England) 39 22278920
2012 Circadian regulation of low density lipoprotein receptor promoter activity by CLOCK/BMAL1, Hes1 and Hes6. Experimental & molecular medicine 39 22913986
2022 Exploring the effect of Weifuchun capsule on the toll-like receptor pathway mediated HES6 and immune regulation against chronic atrophic gastritis. Journal of ethnopharmacology 36 36403744
2017 LncSHRG promotes hepatocellular carcinoma progression by activating HES6. Oncotarget 32 29050307
2006 The bHLH transcription factors, Hes6 and Mash1, are expressed in distinct subsets of cells within adult mouse taste buds. Archives of histology and cytology 32 17031025
2011 HES6 gene is selectively overexpressed in glioma and represents an important transcriptional regulator of glioma proliferation. Oncogene 30 21785461
2000 Expression of hes6, a new member of the Hairy/Enhancer-of-split family, in mouse development. Mechanisms of development 30 10906477
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
2000 Expression of mouse HES-6, a new member of the Hairy/Enhancer of split family of bHLH transcription factors. Mechanisms of development 24 11044617
2006 Basic helix-loop-helix gene Hes6 delineates the sensory hair cell lineage in the inner ear. Developmental dynamics : an official publication of the American Association of Anatomists 23 16534784
2003 Expression of Hes6 and NeuroD in the olfactory epithelium, vomeronasal organ and non-sensory patches. Chemical senses 23 12714442
2023 The novel GATA1-interacting protein HES6 is an essential transcriptional cofactor for human erythropoiesis. Nucleic acids research 21 36929421
2015 HES6 promotes prostate cancer aggressiveness independently of Notch signalling. Journal of cellular and molecular medicine 21 25864518
2013 Interaction and antagonistic roles of NF-κB and Hes6 in the regulation of cortical neurogenesis. Molecular and cellular biology 21 23689134
2007 Inhibition of cortical astrocyte differentiation by Hes6 requires amino- and carboxy-terminal motifs important for dimerization and phosphorylation. Journal of neurochemistry 20 17868320
2005 The conserved WRPW motif of Hes6 mediates proteasomal degradation. Biochemical and biophysical research communications 18 15896295
2022 Recent advances in understanding the role of HES6 in cancers. Theranostics 16 35673577
2003 Detection of differentially expressed HES-6 gene in metastatic colon carcinoma by combination of suppression subtractive hybridization and cDNA library array. Cancer letters 16 12957362
2011 Hes6 is required for the neurogenic activity of neurogenin and NeuroD. PloS one 15 22114720
2007 Hes6 is required for MyoD induction during gastrulation. Developmental biology 14 17950722
2011 Hes6 is required for actin cytoskeletal organization in differentiating C2C12 myoblasts. Experimental cell research 12 21501606
2010 HES6-1 and HES6-2 function through different mechanisms during neuronal differentiation. PloS one 12 21151987
2007 Hes6 controls cell proliferation via interaction with cAMP-response element-binding protein-binding protein in the promyelocytic leukemia nuclear body. The Journal of biological chemistry 12 18160400
2011 Cis-9,trans-11-conjugated linoleic acid promotes neuronal differentiation through regulation of Hes6 mRNA and cell cycle in cultured neural stem cells. Prostaglandins, leukotrienes, and essential fatty acids 10 21723718
2009 Induction of neuronal apoptosis by expression of Hes6 via p53-dependent pathway. Brain research 10 19968968
2012 HES6 enhances the motility of alveolar rhabdomyosarcoma cells. Experimental cell research 9 22982728
2007 HES6 reverses nuclear reprogramming of insulin-producing cells following cell fusion. Biochemical and biophysical research communications 8 17300753
2015 Hairy and Enhancer of Split 6 (Hes6) Deficiency in Mouse Impairs Neuroblast Differentiation in Dentate Gyrus Without Affecting Cell Proliferation and Integration into Mature Neurons. Cellular and molecular neurobiology 7 26105991
2015 Posterior-anterior gradient of zebrafish hes6 expression in the presomitic mesoderm is established by the combinatorial functions of the downstream enhancer and 3'UTR. Developmental biology 5 26596999
2008 Downregulation of Ccnd1 and Hes6 in rat hippocampus after chronic exposure to the antidepressant paroxetine. Acta neuropsychiatrica 5 25384412
2022 ERCC5, HES6 and RORA are potential diagnostic markers of coronary artery disease. FEBS open bio 4 35934844
2015 Sumoylation of Hes6 Regulates Protein Degradation and Hes1-Mediated Transcription. Endocrinology and metabolism (Seoul, Korea) 3 26435136
2009 Expression and association analyses of promoter variants of the neurogenic gene HES6, a candidate gene for mood disorder susceptibility and antidepressant response. Neuroscience letters 3 19481584
2024 <i>HES6</i>knockdown in human hematopoietic precursor cells reduces their <i>in vivo</i> engraftment potential and their capacity to differentiate into erythroid cells, B cells, T cells and plasmacytoid dendritic cells. Haematologica 2 38572564

Missed literature

Know a paper Affinage missed for HES6? Flag it for the maintainers and the community.

No submissions yet.