Affinage

JUND

Transcription factor JunD · UniProt P17535

Length
347 aa
Mass
35.2 kDa
Annotated
2026-06-10
100 papers in source corpus 47 papers cited in narrative 46 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

JUND encodes a constitutively expressed AP-1 family bZIP transcription factor that binds AP-1/TRE sequences as a homodimer or as heterodimer with Fos/Fra partners to trans-activate target promoters (PMID:2504580, PMID:2493644, PMID:1719551, PMID:8415709). Its high basal expression is driven by an octamer-dominated promoter and reinforced by TRE-mediated positive autoregulation (PMID:1714380, PMID:8172655), and it generates two isoforms (JunD-FL and ΔJunD) by alternative translation initiation, with the full-length form carrying a JNK docking domain and acting as the stronger activator (PMID:12052834, PMID:12105216). Unlike c-Jun, JunD escapes efficient ubiquitination and is correspondingly stable, a difference mapping to the c-Jun N-terminal delta-domain (PMID:8922589). JunD is activated by MAPK signaling — phosphorylated by JNK at N-terminal sites and by ERK1/2 at Ser-100 — to drive transcription of targets including nur77, ferritin H, and TIMP-1 (PMID:11719525, PMID:12052834, PMID:16007120, PMID:17133482). Functionally JunD opposes c-Jun: it slows proliferation, arrests cells in G0/G1, and suppresses Ras transformation, and its growth-suppressive activity requires direct binding by the MEN1 tumor suppressor menin, which represses JunD transcription in an HDAC-dependent manner and, through a shared peptide-binding pocket revealed by crystallography, blocks JNK-mediated JunD phosphorylation (PMID:8124713, PMID:9989505, PMID:10500243, PMID:12960363, PMID:22327296). Conversely, JunD is the critical JNK substrate driving K-Ras–induced lung tumorigenesis (PMID:34236045). A central physiological role is limitation of oxidative stress: JunD regulates antioxidant defense genes and NADPH oxidase subunits, controlling H2O2/ROS levels, restraining HIF-α/VEGF-A–driven angiogenesis, and protecting the vasculature, heart, liver, and brain from injury (PMID:15369676, PMID:18182393, PMID:23410942, PMID:30626291, PMID:32815777). JunD also mediates TGF-β–induced fibroblast activation and fibrosis via Smad-dependent induction (PMID:17133482, PMID:21515915), regulates macrophage activation and inflammatory cytokine output (PMID:18443593, PMID:23398888), and is post-transcriptionally controlled through polyamine-dependent competitive binding of HuR and AUF1 to its 3'-UTR (PMID:20805360).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1989 High

    Established JUND as a bona fide AP-1 transcription factor, defining its molecular identity as a DNA-binding, TRE-activating protein related to c-Jun.

    Evidence cDNA cloning, DNA-binding and transactivation reporter assays, with c-Fos co-expression

    PMID:2493644 PMID:2504580

    Open questions at the time
    • Did not define partner-specific dimer preferences
    • No in vivo target genes identified
  2. 1991 High

    Showed that JunD has functions opposite to c-Jun — it suppresses proliferation and Ras transformation — framing JunD as a growth-suppressive AP-1 member, and identified the constitutive high-expression promoter.

    Evidence Retroviral overexpression in NIH 3T3 with cell-cycle and transformation assays; promoter deletion/mutagenesis

    PMID:1714380 PMID:8124713

    Open questions at the time
    • Mechanism of growth suppression not defined at this stage
    • Did not identify the menin requirement later established
  3. 1996 High

    Explained why JunD is more stable than c-Jun by showing it escapes efficient ubiquitination, mapping the difference to the c-Jun delta-domain.

    Evidence Ubiquitination assays, protein stability measurements, chimeric/deletion mutants

    PMID:8922589

    Open questions at the time
    • E3 ligase machinery not identified
    • Did not connect stability to specific physiological outputs
  4. 1999 High

    Identified menin (MEN1) as a direct, JunD-specific repressor, linking JunD growth suppression to a tumor-suppressor pathway and showing repression is HDAC-dependent.

    Evidence Yeast two-hybrid, reciprocal in vitro/in vivo binding, reporter assays, MEN1 mutant panel, TSA treatment

    PMID:10500243 PMID:9989505

    Open questions at the time
    • Structural basis of binding not yet defined
    • Did not establish whether menin binding is required for growth suppression
  5. 2000 High

    Genetic knockout established physiological JunD functions: protection against p53-dependent senescence/apoptosis and a specific role in male reproduction, with no Jun-family compensation.

    Evidence JunD-/- mice and primary fibroblasts; senescence, UV/TNF apoptosis, hepatitis models; histology

    PMID:10654608 PMID:11106750

    Open questions at the time
    • Molecular targets mediating p53/p19Arf control not defined
    • Tissue-specific mechanisms distinct
  6. 2002 High

    Defined the kinase-substrate logic of JunD activation — JNK docking/phosphorylation and isoform-specific potency — and showed menin uncouples MAPK activation from JunD phosphorylation downstream of ERK/JNK.

    Evidence In vitro kinase assays, docking-domain and start-codon mutagenesis, menin deletion mutants

    PMID:12052834 PMID:12105216 PMID:12226747

    Open questions at the time
    • Endogenous stoichiometry of the two isoforms in tissues unclear
    • Precise mechanism by which menin blocks phosphorylation not yet structural
  7. 2003 High

    Established menin binding as required for JunD's anti-proliferative function and showed JunD mediates JNK-driven survival signaling, positioning JunD at a switch between growth suppression and survival.

    Evidence Menin-binding-deficient JunD mutant in Men1-null/JunD-null fibroblasts; JunD KO with JNK/NF-κB analysis; nephron-reduction model with EGFR rescue

    PMID:12820962 PMID:12960363 PMID:12975469

    Open questions at the time
    • Target genes downstream of the JunD survival program incompletely defined
    • How menin binding toggles JunD output mechanistically unresolved at this stage
  8. 2004 High

    Revealed JunD as a master regulator of oxidative stress, controlling antioxidant genes and ROS to restrain HIF-α/VEGF-A angiogenesis, defining its protective vascular/anti-tumor role.

    Evidence junD-/- cells, ROS/PHD activity assays, HIF-α/VEGF-A measurement, iron chelation; ferritin H ARE ChIP and Ser-100 phosphorylation

    PMID:15369676 PMID:16007120

    Open questions at the time
    • Full antioxidant gene repertoire not enumerated
    • Relative contribution of each redox target uncertain
  9. 2008 High

    Extended JunD function to fibrosis, inflammation, and barrier regulation, and revealed dual transcriptional and post-transcriptional control mechanisms.

    Evidence junD-/- fibrosis models, macrophage siRNA in rat/human, ZO-1 promoter/3'-UTR (TIAR) analysis, liver I/R with JNK1 dominant-negative rescue

    PMID:17133482 PMID:18182393 PMID:18443593 PMID:18562690

    Open questions at the time
    • Tissue-specific dimer partners not fully mapped
    • Crosstalk between transcriptional and translational repression unresolved
  10. 2010 High

    Defined post-transcriptional regulation of JunD by competitive HuR/AUF1 binding to its 3'-UTR in a polyamine-dependent manner, and identified AR-JunD complexes driving polyamine-oxidase-linked ROS.

    Evidence RNA-IP, HuR/AUF1 silencing, polyamine depletion/repletion; AR co-IP, ChIP at SSAT promoter, ROS assays

    PMID:20460526 PMID:20805360

    Open questions at the time
    • 3'-UTR cis-elements for HuR/AUF1 not finely mapped
    • Generality of AR-JunD interaction beyond prostate cells unclear
  11. 2012 High

    Solved the structural basis of menin-JUND regulation, showing menin uses one pocket to bind JUND or MLL1, blocking JNK phosphorylation of JUND while promoting MLL1 transcription.

    Evidence X-ray crystallography of menin–JUND/MLL1 complexes, kinase and reporter assays

    PMID:22327296

    Open questions at the time
    • Does not resolve dynamics of competition with MLL1 in cells
    • In vivo consequences of pocket occupancy not directly tested
  12. 2013 High

    Genome-wide profiling and vascular studies cemented JunD as the central regulator linking antioxidant defense, NADPH oxidase, and inflammation to age-related endothelial dysfunction.

    Evidence ChIP-Seq/transcriptomics in macrophages; JunD-/- and overexpression in mice/human endothelial cells, eNOS/ROS/senescence assays, promoter methylation

    PMID:23398888 PMID:23410942

    Open questions at the time
    • Causal direct vs indirect targets among bound genes not fully separated
    • Mechanism coupling promoter hypermethylation to menin binding incompletely defined
  13. 2021 High

    Demonstrated that JunD, not c-Jun, is the essential JNK/AP-1 substrate required for Ras-driven lung tumorigenesis, clarifying the oncogenic versus suppressive division within the AP-1 family.

    Evidence Conditional c-Jun and JunD knockouts in K-RasG12D lung model, JNK transgene epistasis, phosphorylation analysis

    PMID:34236045

    Open questions at the time
    • Critical JunD transcriptional targets driving tumorigenesis not defined
    • Context-dependence relative to JunD's growth-suppressive role unresolved
  14. 2022 High

    Extended JunD direct-target repertoire to disease-promoting noncoding and metabolic genes, including linc00976 in cholangiocarcinoma and PPARγ in obese hearts.

    Evidence ChIP/ChIP-PCR at linc00976 and PPARγ promoters, luciferase assays, cardiac JunD overexpression/KO, miRNA targeting

    PMID:30629164 PMID:36400758

    Open questions at the time
    • Dimer composition at these promoters not defined
    • Tissue-selectivity of JunD pro-disease versus protective output unexplained

Open questions

Synthesis pass · forward-looking unresolved questions
  • How JunD's opposing activities — growth suppression versus Ras-driven tumorigenesis, vascular protection versus pro-fibrotic/pro-disease transcription — are switched by dimer partner choice, phosphorylation state, and menin occupancy in a given tissue remains unresolved.
  • No unified model linking partner selection to context-specific output
  • Direct genome-wide targets across tissues not comprehensively defined
  • Predictive rules for when JunD protects versus promotes disease unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 10 GO:0003677 DNA binding 4
Localization
GO:0005634 nucleus 4
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-162582 Signal Transduction 5 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3
Partners
ARFOSFOSL2HBZHIF1AJUNMEN1SP1
Complex memberships
AP-1 (JunD homodimer / Jun-Fos heterodimer)

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 JunD (jun-D) encodes a transcription factor with a DNA-binding domain homologous to c-Jun and JunB, binds AP-1/TRE sequences, and can trans-activate TRE-containing promoters; activation is further enhanced by c-Fos co-expression. cDNA cloning, DNA-binding assays with truncated proteins, transactivation reporter assays The EMBO journal High 2493644 2504580
1991 JunD homodimerizes and binds a cAMP/phorbol ester/Ca2+-inducible enhancer in the proenkephalin gene, activating its transcription in a protein kinase A-dependent manner; JunB inhibits this JunD-mediated activation. Transient transfection reporter assays, DNA-binding assays demonstrating homodimer binding, co-expression experiments Proceedings of the National Academy of Sciences of the United States of America High 1719551
1991 JunD overexpression results in slower growth and accumulation of cells in G0/G1, whereas c-Jun overexpression promotes S/G2/M; JunD partially suppresses Ras-induced transformation, opposing c-Jun function. Retroviral overexpression in NIH 3T3 fibroblasts, cell cycle analysis, focus/soft-agar transformation assay Cell High 8124713
1991 The high constitutive expression of junD is driven by an octamer motif in its promoter, which is the major determinant of basal promoter activity; SP1, CAAT box, Zif268, and TRE-like elements contribute lesser roles. Promoter cloning, deletion analysis, transient transfection reporter assays, mutagenesis of cis-elements The EMBO journal Medium 1714380
1991 Unlike c-Jun (which undergoes multi-ubiquitination and rapid degradation), JunD is not efficiently ubiquitinated and has a correspondingly longer half-life; this difference maps to the N-terminal delta-domain of c-Jun. Ubiquitination assays, protein stability measurements, N-terminal deletion/chimeric mutant analysis Biological chemistry High 8922589
1992 JunD (together with c-Jun) transactivates the human c-myb promoter via an AP-1-like element at -149; JunB does not. Antisense oligonucleotides to junD inhibit T-lymphocyte proliferation and reduce c-myb mRNA. Transient transfection reporter assays, gel-shift/supershift assays, site-directed mutagenesis of AP-1 element, antisense oligonucleotide treatment The Journal of biological chemistry Medium 1527086
1993 JunD mutants with spontaneously acquired transforming activity show enhanced transactivation specifically when forming heterodimers with Fra-2, but not with c-Fos or Fra-1; the mutated regions function as transactivation domains in a partner-specific manner. Retroviral mutagenesis, transformation assays, transient reporter assays with Fos/Fra family co-expression Proceedings of the National Academy of Sciences of the United States of America Medium 8415709
1994 JunD is identified as the key mediator of nur77 induction by NGF and membrane depolarization in PC12 cells: JunD binds NAP1/NAP2 AP-1-like elements in the nur77 promoter, transactivates through them, and a dominant-negative JunD abolishes nur77 activation by both stimuli. Nuclear extract binding assays (EMSA/supershift), transient reporter transfection, dominant-negative JunD expression Molecular and cellular biology High 7969116
1994 JunD positively auto-regulates its own promoter through its unique TRE element, creating a positive autoregulatory loop that may account for its constitutive expression. Promoter-reporter transfection assays comparing junD vs. c-jun/junB transactivation of hjunD promoter constructs DNA and cell biology Medium 8172655
1999 Menin (MEN1 tumor suppressor) directly interacts with JunD and represses JunD-activated transcription. Menin does not directly interact with other Jun or Fos family members. Several MEN1 missense mutations disrupt menin–JunD interaction. Yeast two-hybrid screen, in vitro binding assay, in vivo co-immunoprecipitation, Gal4-fusion reporter and AP-1-responsive reporter assays, MEN1 missense mutant panel Cell High 10500243 9989505
1999 Menin-mediated repression of JunD transcriptional activity is dependent on histone deacetylase activity: the HDAC inhibitor trichostatin A relieves menin-dependent repression of JunD. Co-transfection reporter assays, trichostatin A treatment, C-terminal deletion mutants of menin Biochimica et biophysica acta Medium 10500243
1999 TGF-β1 induces IL-6 expression in primary human lung fibroblasts via an AP-1 site; the TGF-β1-activated AP-1 complex is a JunD homodimer (absent of Fos isoforms), as shown by supershift analysis. EMSA supershift analysis, luciferase reporter with 5'-deletions and site-directed mutagenesis, RT-PCR, ELISA The Journal of biological chemistry Medium 10212284
2000 JunD-deficient primary fibroblasts exhibit p53-dependent growth arrest, upregulated p19Arf, and premature senescence. JunD also protects against p53-dependent apoptosis in response to UV irradiation and TNF-α in vivo. JunD knockout mouse-derived primary fibroblasts, senescence assays, UV/TNF apoptosis assays, in vivo TNF-mediated hepatitis model Molecular cell High 11106750
2000 Targeted disruption of murine junD causes multiple age-dependent defects in male reproductive function and impaired spermatogenesis, demonstrating specific in vivo functions. JunD-/- animals are viable, with no compensatory upregulation of c-Jun or JunB. Gene targeting (lacZ knock-in), histology, hormone assays, spermatogenesis analysis Development (Cambridge, England) High 10654608
2001 JunD regulates TIMP-1 gene promoter activity in activated hepatic stellate cells, acting primarily as JunD homodimers; JunD also activates IL-6 transcription as a heterodimer at an alternative AP-1 site. Expression vectors for wild-type, dominant-negative, and forced-homodimer JunD/eb1 chimeras; AP-1 EMSA from activated HSCs; promoter-reporter and mutagenesis assays The Journal of biological chemistry High 11337499
2001 PGF2α induces JunD phosphorylation via a calcium/calmodulin-dependent activation of ERK1/2; JunD bound constitutively to AP-1 sites in the nur77 promoter is activated by this phosphorylation to induce nur77 and 20α-HSD gene expression. Serial 5'-deletion promoter assays, dominant-negative JunD, AP-1 site mutagenesis, calcium/calmodulin and ERK inhibitors, in vitro kinase assays The Journal of biological chemistry High 11719525
2002 Both JunD isoforms (full-length JunD-FL and truncated ΔJunD, generated by alternative translation initiation) are phosphorylated by JNK at three identical residues; JunD-FL contains a JNK docking domain, binds JNK more efficiently, and is a more potent transcriptional activator than ΔJunD. In vitro kinase assays, docking domain mutagenesis, transcriptional reporter assays, site-directed mutagenesis of JNK phosphorylation sites The Journal of biological chemistry High 12052834
2002 JunD mRNA produces two protein isoforms (JunD-FL 39 kDa and ΔJunD 34 kDa) by alternative translation initiation from two in-frame AUGs; the 5'-UTR structure regulates the ratio of the two isoforms, and translation is cap-dependent (no IRES). Translational reporter assays, mutagenesis of start codons (AUG, ACG, CUG), cap-dependent translation assay The Journal of biological chemistry High 12105216
2002 Menin inhibits ERK-dependent phosphorylation of JunD and JNK-mediated phosphorylation of JunD and c-Jun without affecting upstream ERK2 or JNK1 activation, acting downstream of MAPK to uncouple kinase activation from nuclear target phosphorylation; two distinct inhibitory mechanisms for ERK and JNK pathways are indicated by N-terminal deletion analysis. In vitro kinase assays, overexpression of Menin, N-terminal deletion mutants of Menin, phosphorylation analysis Oncogene High 12226747
2003 JNK-stimulated survival signaling is mediated by JunD; the JNK/JunD pathway collaborates with NF-κB to increase antiapoptotic gene expression, providing a mechanistic basis for dual JNK roles in apoptosis versus survival. Genetic mouse models (JunD KO), JNK signaling pathway analysis, NF-κB activity assays, antiapoptotic gene expression analysis Molecular cell High 12820962
2003 JunD transcription factor switches from growth suppressor to growth promoter when its binding to menin is prevented (either by a JunD G42E mutant unable to bind menin or by Men1-null background), demonstrating that menin interaction is required for JunD's anti-proliferative function. Stable cell lines with wild-type or menin-binding-deficient JunD mutant in JunD-/- or Men1-/- immortalized fibroblasts; proliferation assays; morphological analysis; cyclin D1 measurement Proceedings of the National Academy of Sciences of the United States of America High 12960363
2003 JunD is required to halt a second wave of cell proliferation and prevent glomerular sclerosis and fibrosis after nephron reduction; the effect is non-cell-autonomous and involves upregulation of the paracrine mitogen TGF-α (EGFR ligand). JunD-/- mice with 75% nephron reduction, bitransgenic JunD-/-/REM (dominant-negative EGFR) rescue, TGF-α expression analysis The Journal of clinical investigation High 12975469
2004 JunD limits tumor angiogenesis by regulating antioxidant defense genes, reducing H2O2 production. In junD-/- cells, H2O2 accumulation decreases FeII availability, reduces HIF prolyl hydroxylase (PHD) activity, leading to HIF-α accumulation and VEGF-A transcription. junD-/- cell lines, ROS measurement, PHD activity assays, HIF-α western blot, VEGF-A expression, iron chelation experiments Cell High 15369676
2004 HBZ (HTLV-1 bZIP factor) interacts with JunD via the bZIP domains of both proteins in vitro and in vivo, and this interaction activates JunD-dependent transcription (in contrast to HBZ's repression of c-Jun). Co-immunoprecipitation (in vivo), in vitro binding assay, co-transfection reporter assays FEBS letters Medium 15044019
2004 JunD promotes osteoblast differentiation (upregulating Runx2, COL1, osteocalcin, ALP); menin co-immunoprecipitates with JunD in osteoblasts, and menin overexpression suppresses JunD-induced AP-1 reporter activity and alkaline phosphatase activity. Stable overexpression, menin antisense knockdown, co-immunoprecipitation, AP-1 luciferase reporter, ALP activity assay The Journal of biological chemistry Medium 15563473
2005 JunD binds the antioxidant response element (ARE) of the human ferritin H gene, is phosphorylated at Ser-100 by H2O2 or t-BHQ treatment, and activates ferritin H transcription; ChIP confirmed H2O2-induced JunD binding to the ferritin H ARE in vivo. EMSA/gel retardation, chromatin immunoprecipitation (ChIP), phosphorylation analysis, JunD overexpression with endogenous ferritin H protein measurement Oncogene High 16007120
2006 JunD is a profibrogenic transcription factor in liver: junD-/- mice are protected from CCl4-induced fibrosis with reduced TIMP-1 expression; Ser100 phosphorylation of JunD (mediated by ERK1/2, not JNK) regulates JunD-dependent TIMP-1 expression in activated HSCs. junD-/- mice with CCl4 fibrosis model, alpha-SMA immunostaining, TIMP-1 mRNA analysis, phospho-mutant analysis, JNK inhibitor ruling-out experiments Hepatology High 17133482
2007 HBZ and JunD co-occupy the proximal region of the hTERT promoter (via ChIP) and form heterodimers that interact with Sp1; activation of hTERT transcription by HBZ/JunD heterodimers is mediated through Sp1 GC-rich binding sites. Co-transfection luciferase reporter assays, RT-PCR, ChIP, Sp1 co-immunoprecipitation Retrovirology Medium 18078517
2008 JunD is a major determinant of macrophage activation in WKY rats; JunD knockdown in rat and human primary macrophages reduces Fc receptor-mediated macrophage activation and cytokine production, demonstrating conserved function. Congenic mapping, siRNA knockdown in rat and human macrophages, Fc receptor-mediated activation assays, cytokine measurement Nature genetics High 18443593
2008 JunD negatively regulates ZO-1 expression at both transcriptional and translational levels in intestinal epithelial cells: transcriptional repression is mediated through a CREB-binding site in the ZO-1 promoter, and translational repression involves enhanced binding of RNA-binding protein TIA-1-related (TIAR) to the ZO-1 3'-UTR. Ectopic JunD overexpression, polyamine depletion, luciferase reporter with ZO-1 promoter, RNA co-immunoprecipitation for TIAR binding to ZO-1 3'-UTR, epithelial permeability assays Molecular biology of the cell High 18562690
2008 THC activates JunD by upregulating gene expression and translocating the protein to the nuclear compartment, and these events are accompanied by decreased breast cancer cell proliferation; JunD knockdown and genetic ablation reduce THC's antiproliferative effect. siRNA knockdown, JunD KO fibroblasts, nuclear fractionation, RT-PCR/western blot, proliferation assays Oncogene Medium 18454173
2008 JunD protects the liver from ischemia/reperfusion injury by suppressing AP-1 transcriptional activation; in the absence of JunD, c-Jun phosphorylation and AP-1 activation are elevated, correlating with increased caspase activation. JunD counterbalances JNK1 and regulates NADPH oxidase (Nox2/Nox4) expression. JunD-/- mice with I/R model, dominant-negative JNK1 transgene rescue, AP-1 reporter assays, caspase activation assays, Nox2/Nox4 mRNA analysis The Journal of biological chemistry High 18182393
2009 JunD and HIF-1α co-operatively mediate TGF-β1-induced transcriptional activation of the angiotensinogen gene in human lung fibroblasts; both proteins bind the AGT core promoter as shown by oligonucleotide pulldown and ChIP; simultaneous knockdown of both completely eliminates TGF-β1-inducible AGT promoter activity. Oligonucleotide pulldown, ChIP, serial deletion/site-directed mutagenesis of AGT promoter, siRNA knockdown of JunD and HIF-1α, luciferase reporter assays FASEB journal High 19211927
2010 Polyamines regulate JunD mRNA stability by modulating competitive binding of HuR (stabilizing) and AUF1 (destabilizing) to the JunD 3'-UTR: polyamine depletion increases HuR binding and decreases AUF1 association, stabilizing JunD mRNA; HuR silencing prevents polyamine depletion-induced JunD upregulation. RNA-immunoprecipitation, HuR/AUF1 silencing by siRNA, polyamine depletion/repletion experiments, mRNA stability assays Molecular and cellular biology High 20805360
2010 Androgen receptor (AR) forms a complex with JunD in androgen-treated prostate cancer cells (co-immunoprecipitation and Gaussia luciferase reconstitution); JunD binds directly to the SSAT promoter only in androgen-treated LNCaP cells (ChIP), and JunD is essential for androgen-induced SSAT gene expression and the resulting ROS production. Co-immunoprecipitation, Gaussia luciferase reconstitution assay, ChIP, luciferase reporter, JunD-silenced (siRNA) stable cell line, DCF ROS assay Cancer research High 20460526
2011 JunD mediates TGF-β-induced fibroblast activation in systemic sclerosis; JunD overexpression is Smad3/Smad4-dependent (siRNA silencing of Smad3/4 prevents JunD induction). JunD-/- fibroblasts are less responsive to TGF-β and release less collagen; JunD-/- mice are protected from bleomycin-induced fibrosis. siRNA knockdown of Smad3/Smad4, JunD-/- fibroblasts and mice, bleomycin fibrosis model, hydroxyproline assays, alpha-SMA counting Annals of the rheumatic diseases High 21515915
2012 Crystal structures of human menin in complex with MLL1 or JUND reveal that the same deep pocket binds short peptides of MLL1 or JUND in identical manners; menin-JUND interaction blocks JNK-mediated JUND phosphorylation and suppresses JUND-induced transcription, whereas menin promotes MLL1-mediated transcription. X-ray crystallography (crystal structures of free menin, menin–MLL1, menin–JUND, menin–MLL1–LEDGF complexes), kinase phosphorylation assays, transcriptional reporter assays Nature High 22327296
2013 JunD is identified as a primary regulator of oxidative stress and IL-1β synthesis in macrophages via combined ChIP-Seq and transcriptome analysis; JunD binding events correlate with gene expression changes for oxidative stress and inflammatory genes in primary macrophages. ChIP-Seq, microarray transcriptomics after Jund siRNA knockdown, comparative expression in congenic strains with different JunD levels BMC genomics High 23398888
2013 JunD deficiency accelerates age-related endothelial dysfunction by reducing scavenger enzymes (MnSOD, ecSOD, ALDH2) and upregulating NADPH oxidase subunits (p47phox, Nox2, Nox4), leading to mitochondrial superoxide formation, reduced eNOS activity, and premature vascular senescence; old WT mice show reduced JunD due to promoter hypermethylation and increased menin binding. JunD-/- mice (young and old), eNOS activity assays, ESR spectroscopy, NADPH oxidase subunit analysis, telomerase activity, senescence markers, JunD overexpression rescue, siRNA knockdown in human endothelial cells, promoter methylation analysis Circulation High 23410942
2013 BAG3 stabilizes JunD mRNA, contributing to JunD-mediated growth inhibition; c-Jun transcriptionally activates BAG3 expression. BAG3 knockdown/overexpression, mRNA stability assays, proliferation assays Biochimica et biophysica acta Low 24140207
2016 TGF-β reduces JunD protein (not mRNA) in RWPE-1 and DU145 prostate cells via proteasomal degradation, correlating with inhibition of proliferation; selective siRNA knockdown of JunD reduces proliferation while knockdown of c-Jun or JunB has little effect. siRNA knockdown of individual Jun family members, proteasome inhibitor treatment, JunD overexpression, proliferation assays The Journal of biological chemistry Medium 27358408
2019 JunD transcriptional activity is increased in obese hearts; JunD directly binds the PPARγ promoter (ChIP) to drive transcription of TG synthesis/uptake/storage genes (Fas, Cd36, Lpl, Plin5), causing myocardial lipid accumulation; JunD is a direct target of miR-494-3p (Ago2 IP + luciferase assay). ChIP for JunD at PPARγ promoter, Ago2 immunoprecipitation, luciferase reporter assay, cardiac-specific JunD overexpression, JunD-/- DIO mice, miR-494-3p overexpression European heart journal High 30629164
2019 JunD blunts ischemia/reperfusion-induced brain injury by suppressing IL-1β; JunD knockdown increases brain IL-1β and worsens stroke outcomes; anti-IL-1β antibody rescues the deleterious effects of JunD silencing. In vivo siRNA knockdown in mice, MCAO stroke model, brain IL-1β measurement, cytokine panels, anti-IL-1β antibody rescue experiment Stroke High 30626291
2020 Hyperglycemia-induced JunD downregulation in the diabetic myocardium is mediated by a complex epigenetic mechanism involving DNA promoter hypermethylation, histone modifications, and translational repression by miR-673/menin; cardiac-specific JunD overexpression protects against hyperglycemia-induced dysfunction. Streptozotocin diabetes model, cardiac-specific αMHC-JunD transgenic mice, ESR spectroscopy for ROS, echocardiography, promoter methylation analysis, histone mark analysis, miRNA-673 and menin analysis Circulation research High 32815777
2021 JunD (not c-Jun) is the crucial AP-1 substrate of JNK signaling required for Ras-driven lung tumorigenesis: c-Jun deletion increases JunD protein and lung tumor burden; deletion of JunD completely abolishes K-Ras-driven lung adenocarcinoma; phosphorylation of JunD is increased in c-Jun-deficient lung cells. Inducible lung-specific conditional KO (c-Jun and JunD), K-RasG12D lung tumor model, dominant-active JNKK2-JNK1 transgene, tumor burden quantification, JunD phosphorylation analysis JCI insight High 34236045
2022 JunD directly binds the linc00976 promoter and activates its transcription (established by ChIP-PCR), thereby promoting cholangiocarcinoma progression. ChIP-PCR for JunD binding at linc00976 promoter, luciferase reporter assay Cell death & disease Medium 36400758

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1989 jun-D: a third member of the jun gene family. Proceedings of the National Academy of Sciences of the United States of America 543 2493644
1989 Characterization of junD: a new member of the jun proto-oncogene family. The EMBO journal 533 2504580
1999 Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription. Cell 501 9989505
2004 JunD reduces tumor angiogenesis by protecting cells from oxidative stress. Cell 491 15369676
1994 Mouse JunD negatively regulates fibroblast growth and antagonizes transformation by ras. Cell 301 8124713
2012 The same pocket in menin binds both MLL and JUND but has opposite effects on transcription. Nature 244 22327296
2000 JunD protects cells from p53-dependent senescence and apoptosis. Molecular cell 218 11106750
2003 JunD mediates survival signaling by the JNK signal transduction pathway. Molecular cell 216 12820962
1998 Peripheral axotomy induces long-term c-Jun amino-terminal kinase-1 activation and activator protein-1 binding activity by c-Jun and junD in adult rat dorsal root ganglia In vivo. The Journal of neuroscience : the official journal of the Society for Neuroscience 199 9454841
1994 Protein kinase A and AP-1 (c-Fos/JunD) are induced during apoptosis of mouse mammary epithelial cells. Oncogene 196 8134124
1995 Basal expression of the inducible transcription factors c-Jun, JunB, JunD, c-Fos, FosB, and Krox-24 in the adult rat brain. The Journal of comparative neurology 180 7615874
1995 Fos-related antigen (Fra-1), junB, and junD activate human involucrin promoter transcription by binding to proximal and distal AP1 sites to mediate phorbol ester effects on promoter activity. The Journal of biological chemistry 179 7759510
1999 Transforming growth factor-beta1 induces interleukin-6 expression via activating protein-1 consisting of JunD homodimers in primary human lung fibroblasts. The Journal of biological chemistry 174 10212284
2003 Constitutive activation of nuclear factor kappaB p50/p65 and Fra-1 and JunD is essential for deregulated interleukin 6 expression in prostate cancer. Cancer research 162 12727841
1991 Overexpression of c-jun, junB, or junD affects cell growth differently. Proceedings of the National Academy of Sciences of the United States of America 156 1924349
1991 cAMP-dependent regulation of proenkephalin by JunD and JunB: positive and negative effects of AP-1 proteins. Proceedings of the National Academy of Sciences of the United States of America 153 1719551
1995 Differential expression of the fos and jun family members c-fos, fosB, Fra-1, Fra-2, c-jun, junB and junD during human epidermal keratinocyte differentiation. Oncogene 121 8545126
2009 Epidermal growth factor receptor and PTEN modulate tissue factor expression in glioblastoma through JunD/activator protein-1 transcriptional activity. Cancer research 114 19276385
2004 HBZ interacts with JunD and stimulates its transcriptional activity. FEBS letters 110 15044019
2000 Targeted disruption of the murine junD gene results in multiple defects in male reproductive function. Development (Cambridge, England) 108 10654608
2000 Regulation of AP1 (Jun/Fos) factor expression and activation in ovarian granulosa cells. Relation of JunD and Fra2 to terminal differentiation. The Journal of biological chemistry 106 10934195
2005 JunD activates transcription of the human ferritin H gene through an antioxidant response element during oxidative stress. Oncogene 105 16007120
2003 Transcription factor JunD, deprived of menin, switches from growth suppressor to growth promoter. Proceedings of the National Academy of Sciences of the United States of America 103 12960363
2019 Obesity-induced activation of JunD promotes myocardial lipid accumulation and metabolic cardiomyopathy. European heart journal 102 30629164
2007 HTLV-1 HBZ cooperates with JunD to enhance transcription of the human telomerase reverse transcriptase gene (hTERT). Retrovirology 102 18078517
1999 Menin represses JunD-activated transcription by a histone deacetylase-dependent mechanism. Biochimica et biophysica acta 101 10500243
2001 A calcium/calmodulin-dependent activation of ERK1/2 mediates JunD phosphorylation and induction of nur77 and 20alpha-hsd genes by prostaglandin F2alpha in ovarian cells. The Journal of biological chemistry 96 11719525
2004 JunD regulates lymphocyte proliferation and T helper cell cytokine expression. The EMBO journal 92 15029240
2013 Deletion of the activated protein-1 transcription factor JunD induces oxidative stress and accelerates age-related endothelial dysfunction. Circulation 90 23410942
2001 JunD regulates transcription of the tissue inhibitor of metalloproteinases-1 and interleukin-6 genes in activated hepatic stellate cells. The Journal of biological chemistry 84 11337499
2002 Menin uncouples Elk-1, JunD and c-Jun phosphorylation from MAP kinase activation. Oncogene 82 12226747
2008 Jund is a determinant of macrophage activation and is associated with glomerulonephritis susceptibility. Nature genetics 78 18443593
2002 JunD stabilization results in inhibition of normal intestinal epithelial cell growth through P21 after polyamine depletion. Gastroenterology 78 12198703
2021 Sodium/glucose cotransporter 2 (SGLT2) inhibitors improve cardiac function by reducing JunD expression in human diabetic hearts. Metabolism: clinical and experimental 77 34801581
2007 TCDD deregulates contact inhibition in rat liver oval cells via Ah receptor, JunD and cyclin A. Oncogene 72 17952121
2006 JunD/AP-1 and STAT3 are the major enhancer molecules for high Bcl6 expression in germinal center B cells. International immunology 69 16702165
2008 JunD represses transcription and translation of the tight junction protein zona occludens-1 modulating intestinal epithelial barrier function. Molecular biology of the cell 68 18562690
2014 A time- and matrix-dependent TGFBR3-JUND-KRT5 regulatory circuit in single breast epithelial cells and basal-like premalignancies. Nature cell biology 66 24658685
2019 AP-1 (Activated Protein-1) Transcription Factor JunD Regulates Ischemia/Reperfusion Brain Damage via IL-1β (Interleukin-1β). Stroke 65 30626291
2015 MicroRNA-494 inhibition protects nucleus pulposus cells from TNF-α-induced apoptosis by targeting JunD. Biochimie 62 25906693
2010 Jun and JunD-dependent functions in cell proliferation and stress response. Cell death and differentiation 61 20300111
2011 The transcription factor JunD mediates transforming growth factor {beta}-induced fibroblast activation and fibrosis in systemic sclerosis. Annals of the rheumatic diseases 59 21515915
2008 JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene 59 18454173
2005 Lack of JunD promotes pressure overload-induced apoptosis, hypertrophic growth, and angiogenesis in the heart. Circulation 59 16129800
2010 Polyamines regulate the stability of JunD mRNA by modulating the competitive binding of its 3' untranslated region to HuR and AUF1. Molecular and cellular biology 58 20805360
2003 JunD protects against chronic kidney disease by regulating paracrine mitogens. The Journal of clinical investigation 58 12975469
1999 Extracellular signal-regulated kinase 1/2-mediated phosphorylation of JunD and FosB is required for okadaic acid-induced activator protein 1 activation. The Journal of biological chemistry 57 9873060
2020 Hyperglycemia Induces Myocardial Dysfunction via Epigenetic Regulation of JunD. Circulation research 56 32815777
2002 Translational regulation of the JunD messenger RNA. The Journal of biological chemistry 56 12105216
1991 Characterization of the mouse junD promoter--high basal level activity due to an octamer motif. The EMBO journal 56 1714380
1994 Involvement of JunD in transcriptional activation of the orphan receptor gene nur77 by nerve growth factor and membrane depolarization in PC12 cells. Molecular and cellular biology 54 7969116
2004 Menin suppresses osteoblast differentiation by antagonizing the AP-1 factor, JunD. The Journal of biological chemistry 50 15563473
2002 Ultraviolet-induced junD activation and apoptosis in myeloblastic leukemia ML-1 cells. The Journal of biological chemistry 46 12082101
1996 Induction of c-fos, c-jun, junB and junD mRNA and AP-1 by alkylating mutagens in cells deficient and proficient for the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) and its relationship to cell death, mutation induction and chromosomal instability. Oncogene 46 8934539
1992 The Jun family members, c-Jun and JunD, transactivate the human c-myb promoter via an Ap1-like element. The Journal of biological chemistry 46 1527086
2022 JUND/linc00976 promotes cholangiocarcinoma progression and metastasis, inhibits ferroptosis by regulating the miR-3202/GPX4 axis. Cell death & disease 45 36400758
2019 Essential role of JunD in cell proliferation is mediated via MYC signaling in prostate cancer cells. Cancer letters 45 30763715
2007 Role of c-Fos/JunD in protecting stress-induced cell death. Cell proliferation 45 17531086
2009 Decreased Jun-D and myogenin expression in muscle wasting of human cachexia. American journal of physiology. Endocrinology and metabolism 44 19470832
2002 Regulation of two JunD isoforms by Jun N-terminal kinases. The Journal of biological chemistry 43 12052834
2006 JunD is a profibrogenic transcription factor regulated by Jun N-terminal kinase-independent phosphorylation. Hepatology (Baltimore, Md.) 42 17133482
2004 Transfection of the multiple endocrine neoplasia type 1 gene to a human endocrine pancreatic tumor cell line inhibits cell growth and affects expression of JunD, delta-like protein 1/preadipocyte factor-1, proliferating cell nuclear antigen, and QM/Jif-1. The Journal of clinical endocrinology and metabolism 42 15126560
2005 Curcumin suppresses constitutive activation of AP-1 by downregulation of JunD protein in HTLV-1-infected T-cell lines. Leukemia research 41 16157375
1998 Three activator protein-1-binding sites bound by the Fra-2.JunD complex cooperate for the regulation of murine laminin alpha3A (lama3A) promoter activity by transforming growth factor-beta. The Journal of biological chemistry 41 9651314
2016 MicroRNA-663a is downregulated in non-small cell lung cancer and inhibits proliferation and invasion by targeting JunD. BMC cancer 40 27184257
2012 Thyroid hormone limits postnatal Sertoli cell proliferation in vivo by activation of its alpha1 isoform receptor (TRalpha1) present in these cells and by regulation of Cdk4/JunD/c-myc mRNA levels in mice. Biology of reproduction 40 22539677
1997 C-Jun and JunD suppress maturation of chondrocytes. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 40 9149901
2020 LncRNA LOXL1-AS1 is transcriptionally activated by JUND and contributes to osteoarthritis progression via targeting the miR-423-5p/KDM5C axis. Life sciences 39 32679142
2004 Constitutive expression of the AP-1 transcription factors c-jun, junD, junB, and c-fos and the marginal zone B-cell transcription factor Notch2 in splenic marginal zone lymphoma. The Journal of molecular diagnostics : JMD 39 15507668
2013 Combined ChIP-Seq and transcriptome analysis identifies AP-1/JunD as a primary regulator of oxidative stress and IL-1β synthesis in macrophages. BMC genomics 38 23398888
2008 A genomic and expression study of AP-1 in primary cutaneous T-cell lymphoma: evidence for dysregulated expression of JUNB and JUND in MF and SS. Journal of cutaneous pathology 38 18494816
2002 Luteinizing hormone-releasing hormone induces JunD-DNA binding and extends cell cycle in human ovarian cancer cells. Biochemical and biophysical research communications 38 12054733
2008 JunD mediates androgen-induced oxidative stress in androgen dependent LNCaP human prostate cancer cells. The Prostate 37 18386285
2007 Induced JunD in intestinal epithelial cells represses CDK4 transcription through its proximal promoter region following polyamine depletion. The Biochemical journal 37 17253961
2001 Nerve growth factor, but not epidermal growth factor, increases Fra-2 expression and alters Fra-2/JunD binding to AP-1 and CREB binding elements in pheochromocytoma (PC12) cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 37 11150315
2021 JunD, not c-Jun, is the AP-1 transcription factor required for Ras-induced lung cancer. JCI insight 36 34236045
2009 JunD and HIF-1alpha mediate transcriptional activation of angiotensinogen by TGF-beta1 in human lung fibroblasts. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 36 19211927
2005 Distinct functions of junD in cardiac hypertrophy and heart failure. Genes & development 36 15655111
1996 Differential regulation of c-Jun and JunD by ubiquitin-dependent protein degradation. Biological chemistry 36 8922589
1995 Cyclic AMP stimulates a JunD/Fra-2 AP-1 complex and inhibits the proliferation of interleukin-6-dependent cell lines. Oncogene 35 7566966
1999 Polyamine depletion is associated with an increase in JunD/AP-1 activity in small intestinal crypt cells. The American journal of physiology 34 9950818
1991 Structure and function of human jun-D. Oncogene 34 1903194
2016 JunD Is Required for Proliferation of Prostate Cancer Cells and Plays a Role in Transforming Growth Factor-β (TGF-β)-induced Inhibition of Cell Proliferation. The Journal of biological chemistry 32 27358408
2012 The role of heterodimeric AP-1 protein comprised of JunD and c-Fos proteins in hematopoiesis. The Journal of biological chemistry 32 22822070
2008 Hoxc6 is overexpressed in gastrointestinal carcinoids and interacts with JunD to regulate tumor growth. Gastroenterology 32 18655788
1991 The chicken junD gene and its product. Oncogene 32 1923529
2019 JUND regulates pancreatic β cell survival during metabolic stress. Molecular metabolism 31 31023625
2006 JunD attenuates phenylephrine-mediated cardiomyocyte hypertrophy by negatively regulating AP-1 transcriptional activity. Cardiovascular research 31 16690042
1994 The human junD gene is positively and selectively autoregulated. DNA and cell biology 31 8172655
1998 Decreased transcription factor junD in brains of patients with Down syndrome. Neuroscience letters 30 9739985
1995 Comparison of c-jun, junB, and junD mRNA expression and protein in the rat dorsal root ganglia following sciatic nerve transection. Journal of neuroscience research 30 8583508
1993 JunD mutants with spontaneously acquired transforming potential have enhanced transactivating activity in combination with Fra-2. Proceedings of the National Academy of Sciences of the United States of America 30 8415709
2010 Androgen receptor requires JunD as a coactivator to switch on an oxidative stress generation pathway in prostate cancer cells. Cancer research 29 20460526
2008 JunD suppresses bone formation and contributes to low bone mass induced by estrogen depletion. Journal of cellular biochemistry 29 18240141
2020 Enhanced JunD/RSK3 signalling due to loss of BRD4/FOXD3/miR-548d-3p axis determines BET inhibition resistance. Nature communications 27 31937753
2018 The miR206-JunD Circuit Mediates the Neurotoxic Effect of Methylmercury in Cortical Neurons. Toxicological sciences : an official journal of the Society of Toxicology 27 29522201
2008 JunD protects the liver from ischemia/reperfusion injury by dampening AP-1 transcriptional activation. The Journal of biological chemistry 27 18182393
1995 Increased transforming activity of JunB and JunD by introduction of an heterologous homodimerization domain. Oncogene 27 7845674
2013 BAG3 is upregulated by c-Jun and stabilizes JunD. Biochimica et biophysica acta 26 24140207
2011 JunD-mediated repression of GADD45α and γ regulates escape from cell death in prostate cancer. Cell cycle (Georgetown, Tex.) 25 21734453

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