Affinage

JUN

Transcription factor Jun · UniProt P05412

Round 2 corrected
Length
331 aa
Mass
35.7 kDa
Annotated
2026-04-28
130 papers in source corpus 51 papers cited in narrative 49 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

c-Jun is a basic leucine-zipper (bZIP) transcription factor that constitutes the core DNA-binding subunit of the AP-1 complex, functioning as a master regulator of cell proliferation, apoptosis, differentiation, and tissue morphogenesis (PMID:2825349, PMID:10072388, PMID:8371760). c-Jun homodimerizes or heterodimerizes with Fos, ATF/CREB, and NFAT family members through its leucine zipper to bind TRE/AP-1 DNA elements, and its transcriptional output is diversified by physical interactions with non-bZIP partners including Smad3/4, STAT3, YAP/TAZ-TEAD, and PU.1 (PMID:7816143, PMID:9732876, PMID:26258633, PMID:9988737). Activity is governed by a multisite phosphorylation code: JNK-mediated phosphorylation of Ser63/Ser73 and Thr91/Thr93 enhances transactivation and simultaneously stabilizes the protein by inhibiting ubiquitin-dependent degradation via a CUL4A/DDB1/DET1/COP1 E3 ligase that targets the delta domain, while GSK3-mediated C-terminal phosphorylation suppresses DNA binding (PMID:8224842, PMID:8994040, PMID:14739464, PMID:12881422). Genetically, c-Jun is essential for hepatogenesis and hepatocyte survival through repression of p53, for eyelid closure via EGFR/HB-EGF regulation, for limb joint specification via Wnt9a/Wnt16, and for Schwann-cell-driven axonal regeneration via GDNF/Artemin transcription (PMID:12553907, PMID:12791272, PMID:23475960, PMID:22753894).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1987 High

    Establishing the identity of c-Jun as the AP-1 transcription factor resolved a central question in signal-responsive gene regulation by showing that a proto-oncogene product is the sequence-specific DNA-binding component of AP-1.

    Evidence Bacterial expression of c-Jun protein, sequence-specific DNA binding assays, peptide sequencing and antibody cross-reactivity with purified human AP-1

    PMID:2825349 PMID:3347253

    Open questions at the time
    • Dimerization partners and DNA-element selectivity not yet defined
    • Post-translational regulation unknown
  2. 1991 High

    Demonstrating that c-Jun heterodimerizes with Fos and ATF/CREB family members via the leucine zipper, with each combination yielding distinct DNA-binding specificities, established the combinatorial logic underlying AP-1 target gene selection.

    Evidence Biochemical dimerization assays, EMSA with cross-family heterodimers, domain deletion mutagenesis

    PMID:1827203 PMID:2133107

    Open questions at the time
    • Structural basis of partner selectivity unresolved
    • In vivo relevance of specific heterodimer combinations not tested
  3. 1993 High

    Identification of JNK as a dedicated c-Jun kinase that docks on the transactivation domain and phosphorylates Ser63/Ser73 established the direct signaling link between stress/oncogenic stimuli and AP-1 activation.

    Evidence Molecular cloning of JNK, in vitro kinase assays, site-directed mutagenesis of phosphoacceptor and docking sites, reporter assays

    PMID:8137421 PMID:8224842

    Open questions at the time
    • Relative contributions of JNK1 vs JNK2 in vivo unclear
    • Additional phosphorylation sites not yet mapped
  4. 1993 High

    Gene targeting showed c-Jun is essential for embryonic hepatogenesis in a cell-autonomous manner, establishing the first in vivo requirement for an AP-1 component in organ development.

    Evidence c-jun knockout mice, chimeric analysis with ES cells contributing to all tissues except liver

    PMID:8371760

    Open questions at the time
    • Downstream transcriptional targets in hepatocytes undefined
    • Relationship to apoptosis vs. proliferation defects not separated
  5. 1994 High

    Discovery that c-Jun is degraded via the ubiquitin-proteasome pathway through a delta domain absent in oncogenic v-Jun explained the mechanistic basis for differential stability between proto-oncogene and viral oncoprotein.

    Evidence In vivo ubiquitination assays with tagged ubiquitin, delta-domain transfer to heterologous substrates, pulse-chase stability measurements

    PMID:8087846

    Open questions at the time
    • Identity of the E3 ubiquitin ligase unknown
    • Relationship between phosphorylation and ubiquitination not established
  6. 1995 High

    Demonstrating intramolecular crosstalk whereby N-terminal phosphorylation promotes C-terminal dephosphorylation to activate DNA binding revealed an allosteric regulatory mechanism within c-Jun.

    Evidence Phosphorylation-site mutagenesis, DNA-binding assays, phosphopeptide analysis after phorbol ester stimulation

    PMID:7744008

    Open questions at the time
    • Structural basis for conformational change not visualized
    • Phosphatase identity for C-terminal dephosphorylation unknown
  7. 1995 High

    The crystal structure of the c-Fos–c-Jun bZIP heterodimer bound to DNA provided the atomic-level framework for understanding partner-selective dimerization and DNA recognition by AP-1.

    Evidence X-ray crystallography of the bZIP heterodimer–DNA complex

    PMID:7816143

    Open questions at the time
    • Full-length c-Jun structure unknown
    • Structural basis for interactions with non-bZIP partners not addressed
  8. 1997 High

    Linking MAP kinase-mediated phosphorylation to inhibition of c-Jun ubiquitination unified two regulatory axes—activity and stability—under a single signaling input.

    Evidence In vivo ubiquitination assays, pulse-chase stability measurements, pharmacological MAP kinase activation

    PMID:8994040

    Open questions at the time
    • Identity of the E3 ligase still unknown at this point
    • Whether phosphorylation directly blocks ubiquitin conjugation or acts indirectly unresolved
  9. 1998 High

    Physical interaction of Smad3/4 with c-Jun at AP-1 elements demonstrated convergence of TGF-β and MAPK signaling at the level of transcription factor complex assembly, expanding the concept of AP-1 as a signaling integrator.

    Evidence In vitro GST pulldown, co-immunoprecipitation, transient reporter assays, dominant-negative Smad experiments, EMSA

    PMID:10220381 PMID:9732876

    Open questions at the time
    • Genome-wide identification of Smad–Jun co-regulated targets not performed
    • Structural basis of Smad–Jun interaction unknown
  10. 1999 High

    Demonstrating that c-Jun controls fibroblast cell cycle progression by directly repressing p53 transcription resolved the proliferative defect of c-jun−/− cells and identified a non-canonical tumor-suppressor-repressive function.

    Evidence c-jun knockout fibroblasts, p53 promoter reporter assays, AP-1 site mutagenesis, genetic rescue by p53 deletion

    PMID:10072388

    Open questions at the time
    • Whether p53 repression operates in all c-Jun-expressing tissues unknown
    • Other c-Jun targets controlling cell cycle not identified
  11. 2003 High

    Multiple tissue-specific conditional knockouts established that c-Jun governs distinct developmental programs—hepatocyte survival (via p53 antagonism), eyelid closure (via EGFR/HB-EGF), and multisite phosphorylation mapping delineated kinase-specific contributions.

    Evidence Liver-specific and epidermal-specific c-jun conditional knockouts, primary cell assays, phospho-specific antibodies with JNK-null MEFs

    PMID:12553907 PMID:12791272 PMID:12881422

    Open questions at the time
    • Tissue-specific differences in c-Jun target gene repertoires not systematically catalogued
    • Redundancy with JunB/JunD in specific tissues unclear
  12. 2004 High

    Identification of the CUL4A/DDB1/DET1/COP1 E3 ligase complex as the machinery targeting c-Jun for proteasomal degradation filled a long-standing gap in understanding c-Jun turnover.

    Evidence Co-immunoprecipitation of complex subunits, RNAi knockdown of each component stabilizing c-Jun, ubiquitination assays, reporter assays

    PMID:14739464

    Open questions at the time
    • Relationship to delta-domain-dependent ubiquitination not fully reconciled
    • Additional E3 ligases (FBW7) later identified suggest redundancy
  13. 2012 High

    Establishing c-Jun as a master regulator of Schwann cell reprogramming after nerve injury—directly activating GDNF and Artemin to promote axonal regeneration via Ret—expanded c-Jun's role to neural repair.

    Evidence Schwann cell-specific c-jun conditional knockout, ChIP at GDNF/Artemin promoters, neuron-specific Ret knockout phenocopy, recombinant ligand rescue

    PMID:22753894

    Open questions at the time
    • Full set of c-Jun-regulated repair genes in Schwann cells not catalogued
    • Mechanism of c-Jun activation after nerve injury incompletely characterized
  14. 2013 High

    Discovery that c-Jun directly regulates Wnt9a and Wnt16 in joint interzone cells, and that its deletion abolishes joint formation, identified c-Jun as a determinant of skeletal joint specification.

    Evidence Conditional c-jun knockout in limb mesenchyme, ChIP-validated binding to Wnt9a/Wnt16 regulatory elements, transgenic reporter mice

    PMID:23475960

    Open questions at the time
    • Upstream signals activating c-Jun in interzone cells unknown
    • Whether c-Jun is sufficient to induce joint fate not tested
  15. 2015 High

    Genome-wide co-occupancy of YAP/TAZ-TEAD and AP-1 at composite enhancers, with reciprocal genetic dependence for oncogenic growth, revealed that c-Jun/AP-1 is an obligate partner of Hippo pathway effectors in cancer.

    Evidence ChIP-seq for YAP, TAZ, TEAD, c-Jun, c-Fos; co-immunoprecipitation; conditional knockout mouse models

    PMID:26258633

    Open questions at the time
    • Whether YAP/TAZ–AP-1 cooperation is cancer-type specific not resolved
    • Direct structural basis of YAP–c-Jun interaction unknown
  16. 2019 High

    Demonstrating that c-Jun overexpression restores chromatin accessibility at AP-1 motifs and rescues CAR T cells from exhaustion established c-Jun deficiency as a molecular basis of T cell dysfunction.

    Evidence Lentiviral c-Jun overexpression in human CAR T cells, five in vivo tumor models, ATAC-seq chromatin accessibility profiling

    PMID:31802004

    Open questions at the time
    • Mechanism by which c-Jun remodels exhaustion-associated chromatin unclear
    • Optimal c-Jun expression levels for therapeutic application not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Despite extensive characterization, key mechanistic questions remain: the full-length c-Jun structure, the structural basis for interactions with non-bZIP partners (Smad3, STAT3, YAP), the tissue-specific logic of c-Jun target gene selection, and how c-Jun levels are calibrated to distinguish proliferative from apoptotic outcomes.
  • No full-length c-Jun structure available
  • Genome-wide c-Jun target sets across tissues not systematically compared
  • Quantitative thresholds for pro-survival vs. pro-apoptotic c-Jun activity not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0003677 DNA binding 4
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1266738 Developmental Biology 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-1640170 Cell Cycle 2 R-HSA-168256 Immune System 2 R-HSA-5357801 Programmed Cell Death 2
Partners
FOSHDAC3JNK1JNK2NFATC2SMAD3STAT3YAP1
Complex memberships
AP-1 (Jun/ATF)AP-1 (Jun/Fos)Smad3/4-JunYAP/TAZ-TEAD-AP-1

Evidence

Reading pass · 49 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1987 The human proto-oncogene c-Jun encodes a sequence-specific DNA-binding protein with structural and functional properties identical to the transcription factor AP-1; bacterially expressed c-Jun protein bound the AP-1 DNA recognition sequence, and antibodies against v-Jun peptides reacted specifically with purified human AP-1, establishing that c-Jun is AP-1. Bacterial expression of c-Jun, sequence-specific DNA binding assay, partial amino acid sequencing of purified AP-1, antibody cross-reactivity Science High 2825349 3347253
1991 MAP kinases pp54 and pp42/44 specifically phosphorylate two serine residues in the c-Jun amino-terminal transactivation domain (A1 domain), and this phosphorylation positively regulates c-Jun transactivating activity; Ha-Ras induces hyperphosphorylation of the same activation domain sites and correspondingly augments c-Jun-mediated transactivation. In vitro kinase assays with purified MAP kinases, site-directed mutagenesis of phosphoacceptor serines, transactivation reporter assays, phosphopeptide mapping Nature High 1903181 1922387
1993 JNK (c-Jun NH2-terminal kinase), a novel serine/threonine kinase activated by oncoproteins and UV irradiation, binds specifically to the c-Jun transactivation domain and phosphorylates Ser-63 and Ser-73, thereby potentiating c-Jun trans-activation function; binding and phosphorylation are coupled, as phosphorylation results in dissociation of the c-Jun–JNK complex, and mutations disrupting the kinase-binding site attenuate the response to Ha-Ras and UV. Molecular cloning of JNK, in vitro kinase assay, site-directed mutagenesis of c-Jun phosphoacceptor and binding sites, transactivation reporter assays Genes & Development High 8137421 8224842
1994 JNK1 is a MAP kinase-family kinase that is activated by dual phosphorylation at Thr and Tyr in response to UV irradiation and Ha-Ras; it binds directly to the c-Jun transactivation domain and phosphorylates Ser-63 and Ser-73, linking oncogenic and UV stress signals to AP-1 activation. Molecular cloning of JNK1, in vitro kinase assay, phosphopeptide mapping, binding assays Cell High 8137421
1994 JNK2 binds c-Jun approximately 25-fold more efficiently than JNK1 and has a lower Km toward c-Jun; this difference was traced to a small beta-strand-like region near the catalytic pocket that serves as a docking site, explaining how closely related MAP kinases can selectively target distinct substrates. Molecular cloning of JNK2, in vitro binding and kinase assays, chimeric kinase domain swaps, structural modeling Genes & Development High 8001819
1994 c-Jun is degraded via the ubiquitin–proteasome pathway; c-Jun, but not oncogenic v-Jun, is efficiently multiubiquitinated in vivo, and a 27-amino-acid delta domain present in c-Jun but deleted in v-Jun acts as a cis-acting ubiquitination and degradation signal; transfer of the delta domain to beta-galactosidase confers ubiquitination and instability. In vivo ubiquitination assay with molecularly tagged ubiquitin, deletion and transfer mutagenesis, pulse-chase protein stability measurements Cell High 8087846
1991 c-Jun and c-Fos heterodimerize through their leucine-zipper domains to form the AP-1 complex; protein dimerization via parallel leucine-zipper interaction is required for DNA binding, and two clusters of basic amino acids adjacent to the leucine zipper in both Fos and Jun are required for sequence-specific DNA contact. Biochemical dimerization assays, DNA binding and competition assays, domain deletion/mutagenesis Seminars in Cancer Biology High 2133107
1995 Crystal structure of the c-Fos–c-Jun bZIP heterodimer bound to DNA revealed that both subunits form continuous alpha-helices: the C-terminal regions form an asymmetric coiled-coil stabilized by electrostatic interactions that favor heterodimer formation, and the N-terminal basic regions make base-specific contacts in the DNA major groove; the coiled-coil is flexibly joined to the basic regions. X-ray crystallography of bZIP heterodimer–DNA complex Nature High 7816143
1991 Cross-family heterodimers form between Fos/Jun and ATF/CREB family members via leucine-zipper interactions, and these heterodimers display DNA binding specificities distinguishable from parental homodimers, demonstrating that the two families constitute a superfamily whose combinatorial dimerization diversifies transcriptional responses. In vitro dimerization, electrophoretic mobility shift assays, DNA binding specificity analysis Proceedings of the National Academy of Sciences High 1827203
1997 Phosphorylation of c-Jun by MAP kinases reduces its ubiquitination and stabilizes the protein, establishing that signal-dependent phosphorylation controls c-Jun abundance by inhibiting ubiquitin-dependent degradation. In vivo ubiquitination assay, pulse-chase protein stability measurements, pharmacological MAP kinase activation Science High 8994040
1999 c-Jun controls cell cycle progression in fibroblasts by directly binding a variant AP-1 site in the p53 promoter and repressing p53 transcription; loss of c-Jun elevates p53 and its target p21, impairing CDK and E2F activation; deletion of p53 abrogates all proliferation defects of c-jun–/– cells. c-jun knockout mouse fibroblasts, p53 promoter reporter assays, chromatin binding/AP-1 site mutagenesis, genetic rescue by p53 deletion, flow cytometry for cell cycle Genes & Development High 10072388
1993 c-jun is essential for normal hepatogenesis and embryonic development; mice homozygous null for c-jun die at mid-to-late gestation with impaired hepatogenesis and altered fetal liver erythropoiesis; c-jun–/– ES cells contribute to all somatic tissues in chimeras except liver, demonstrating a cell-autonomous requirement for c-Jun in hepatocytes. Gene targeting in ES cells, chimeric mouse analysis, histopathology Nature High 8371760
2003 c-Jun prevents apoptosis in hepatocytes by antagonizing p53 activity; liver-specific c-jun inactivation increases p53 and its target Noxa, inducing apoptosis without affecting proliferation; primary c-jun–/– hepatocytes show increased TNF-α-induced apoptosis that is abolished by concomitant p53 deletion, placing c-Jun upstream of p53 in a pro-survival pathway. Conditional liver-specific knockout mice, chemical hepatocarcinogenesis model, p53/noxa expression analysis, primary hepatocyte apoptosis assays, double-knockout genetic rescue Cell High 12553907
1992 c-Jun physically interacts with MyoD both in vivo and in vitro via the leucine-zipper domain of Jun and the helix-loop-helix region of MyoD; this interaction mediates mutual functional antagonism—c-Jun inhibits MyoD-dependent transactivation of muscle-specific genes, and MyoD suppresses c-Jun transactivation through AP-1 sites. Co-immunoprecipitation, GST pulldown, transient transfection reporter assays, domain deletion mutagenesis Cell High 1310896
1999 Smad3 and Smad4 physically interact with all three Jun family members in vitro; TGF-β signaling induces association of Smad3 with rapidly phosphorylated c-Jun; Smad3 is required for TGF-β-mediated activation through concatamerized AP-1 sites that cannot directly bind Smads, establishing that Smad-Jun interaction mediates TGF-β transcriptional responses through AP-1 elements. In vitro GST pulldown, co-immunoprecipitation, transient transfection luciferase reporter assays, dominant-negative Smad experiments Proceedings of the National Academy of Sciences High 10220381 9732876
1998 Smad3 interacts directly with TRE/AP-1 DNA elements and associates physically with c-Jun; Smad3 and Smad4 cooperate with c-Jun–c-Fos to activate TGF-β-inducible transcription through AP-1 sites, via a TGF-β-induced Smad3–c-Jun interaction and a Smad3–c-Fos interaction, demonstrating convergence of Smad and JNK/MAPK signaling at AP-1 promoter elements. In vitro binding, co-immunoprecipitation, transient transfection reporter assays, EMSA Nature High 9732876
1995 The DNA-binding activity of c-Jun is determined by the phosphorylation state of C-terminal threonine/serine residues; phorbol ester-induced C-terminal dephosphorylation that activates DNA binding is an indirect consequence of a separate N-terminal phosphorylation event, indicating intramolecular signal transduction in which N-terminal phosphorylation alters the accessibility of C-terminal phosphoacceptor sites. Phosphorylation-site mutagenesis, DNA-binding assays, phorbol ester stimulation of cells, phosphopeptide analysis The EMBO Journal High 7744008
2003 Multisite phosphorylation of c-Jun is achieved by distinct kinases at specific residues: JNK isoforms are required and sufficient for phosphorylation of Thr91, Thr93, Ser63, and Ser73 in response to stress stimuli; ERK1/ERK2 can also phosphorylate Ser63/Ser73 in response to phorbol ester and EGF; GSK3 phosphorylates Thr239; and an unidentified kinase phosphorylates Ser243. Phospho-specific antibodies, JNK-deficient and wild-type mouse embryonic fibroblasts and macrophages, pharmacological kinase inhibitors, epistasis analysis The EMBO Journal High 12881422
2004 Human DET1 promotes ubiquitination and proteasomal degradation of c-Jun by assembling a multisubunit E3 ubiquitin ligase complex containing DDB1, CUL4A, ROC1, and COP1; RNAi depletion of any subunit stabilizes c-Jun and increases c-Jun-activated transcription. Co-immunoprecipitation, RNAi knockdown of ligase subunits, ubiquitination assays, transcriptional reporter assays Science High 14739464
1999 The COP9 signalosome activates and stabilizes c-Jun through a JNK-independent pathway; overexpression of signalosome subunit Sgn2 drives de novo assembly of the COP9 complex, increases c-Jun protein levels, and elevates AP-1 transcriptional activity independently of JNK or MKK4. Sgn2 overexpression, co-immunoprecipitation, AP-1 reporter assays, dominant-negative kinase constructs Journal of Biological Chemistry Medium 10585392
2004 Transcriptional repression of c-Jun activity involves a multiprotein repressor complex containing histone deacetylase 3 (HDAC3); MAP kinase-mediated phosphorylation of c-Jun relieves this repression; the viral oncoprotein v-Jun, which lacks the delta domain and is constitutively active, escapes this HDAC3-containing repressor complex. Co-immunoprecipitation of HDAC3 with c-Jun, HDAC inhibitor studies, comparison of c-Jun and v-Jun repression sensitivity, reporter assays Cell Cycle Medium 14712066
2001 c-Jun is acetylated in vivo by p300 at Lys271 in the basic region of its DNA-binding domain; this specific lysine is required for transcriptional repression of c-Jun-activated promoters by adenovirus E1A; E1A repression is p300-dependent and specific to c-Jun (not the related EB1 factor). In vitro and in vivo acetylation assays, site-directed mutagenesis of Lys271, chimeric c-Jun/EB1 constructs, transient transfection reporter assays The EMBO Journal High 11689449
2008 SIRT1 associates with c-Jun in co-immunoprecipitation and inhibits its transcriptional activity; SIRT1 is found at the AP-1 response element in the MMP9 promoter and inhibits histone 3 acetylation at this site; SIRT1-deficient MEFs show increased MMP9 expression, demonstrating that SIRT1 deacetylase activity suppresses c-Jun/AP-1-dependent gene expression. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), luciferase reporter assays, SIRT1 knockout MEFs, RT-PCR and western blotting Biochemical and Biophysical Research Communications Medium 18823944
1999 Stat3 and c-Jun physically interact via the C-terminal region of c-Jun and two regions in Stat3 (within the coiled-coil domain and a portion of the DNA-binding domain); this interaction is required for cooperative transcriptional activation of the α2-macroglobulin enhancer in response to IL-6; point mutations in the Stat3 interaction domains block both physical interaction and cooperative transcription. In vitro binding with recombinant proteins, co-immunoprecipitation in transfected cells, transient transfection reporter assays, point mutagenesis of interaction domains Molecular and Cellular Biology High 10490649
1999 c-Jun functions as a JNK-independent coactivator of the ETS factor PU.1 to transactivate the M-CSF receptor promoter; c-Jun associates with PU.1 via its basic domain interacting with the ETS domain of PU.1; this interaction does not require AP-1 DNA binding, and JNK-mediated phosphorylation of c-Jun on Ser-63/73 does not alter its coactivation of PU.1. Co-immunoprecipitation, domain deletion mutagenesis (basic domain mutants), transient transfection reporter assays, dominant-negative c-Jun experiments Journal of Biological Chemistry Medium 9988737
1998 The retinoblastoma protein Rb binds to c-Jun via the leucine zipper region of c-Jun and the B pocket plus C-terminal domain of Rb, and stimulates c-Jun transcriptional activity from an AP-1 consensus sequence; HPV16 E7, which binds both c-Jun and Rb, inhibits Rb activation of c-Jun; Rb–c-Jun complexes are found in terminally differentiating keratinocytes and early G1 cells. Co-immunoprecipitation, domain mutagenesis, transient transfection reporter assays, E7 competition assays The EMBO Journal Medium 9545246
2007 Nuclear import of c-Jun is mediated by multiple importin-family transport receptors (importin β, transportin, importin 7, importin 9, and importin 13) that each bind directly to a single basic-region nuclear localization signal (NLS) preceding the leucine zipper; importin α inhibits nuclear import of c-Jun; a leucine zipper-dependent, NLS-independent import pathway also exists when c-Jun forms complexes with leucine-zipper partners such as c-Fos. In vitro nuclear import assay in digitonin-permeabilized cells, direct binding assays with recombinant importins, NLS mutagenesis, fluorescent reporter constructs Journal of Biological Chemistry High 17652081
2006 WWOX tumor suppressor physically associates with c-Jun via its first WW domain interacting with the proline-rich motif of c-Jun; MEKK1-induced phosphorylation of c-Jun enhances the WWOX–c-Jun interaction; the WWOX–c-Jun complex localizes predominantly to the cytoplasm; WWOX expression attenuates MEKK1-stimulated c-Jun/AP-1 transcriptional activity, and a WW domain point mutant fails to suppress AP-1. Co-immunoprecipitation, domain mutagenesis (WW domain point mutation), subcellular fractionation, luciferase reporter assays Cancer Research Medium 17178850
1996 c-Jun is required for Ras-induced cellular transformation; c-jun-null fibroblasts expressing activated ras lack AP-1-dependent transcription, lose anchorage independence, contact inhibition, and tumorigenicity; re-expression of c-jun restores these properties, establishing c-Jun as a critical effector of Ras-mediated transformation. c-jun null fibroblasts, activated ras expression, AP-1 reporter assays, soft-agar colony formation, nude mouse tumorigenicity assays Molecular and Cellular Biology High 8754851
1997 Increased c-Jun activity alone is sufficient to trigger apoptotic cell death in NIH 3T3 fibroblasts; c-Jun-induced apoptosis requires both the N-terminal transactivation domain and the C-terminal leucine zipper, implicating transcriptional activity; overexpression of Bcl-2 delays c-Jun-mediated apoptosis; α-fodrin is cleaved by ICE/CED-3 cysteine proteases during c-Jun-induced cell death, and cell-permeable ICE/CED-3 inhibitors prevent the death. Conditional c-Jun/ER fusion protein, serum deprivation assays, Bcl-2 overexpression, domain deletion mutants, caspase inhibitor peptides, α-fodrin cleavage assay The EMBO Journal High 9130714
2003 c-Jun regulates eyelid closure and keratinocyte proliferation through the EGFR signaling axis; epidermal-specific c-jun deletion reduces EGFR and HB-EGF expression in eyelid keratinocytes and primary keratinocyte cultures, causing open eyes at birth (phenocopying EGFR-null mice) and prominent cortical actin bundles; c-Jun also controls EGFR in basal keratinocytes to regulate skin tumor formation. Conditional epidermis-specific c-jun knockout mice, primary keratinocyte culture, EGFR/HB-EGF mRNA and protein analysis, tumor model (K5-SOS-F transgenic mice) Developmental Cell High 12791272
2012 c-Jun in Schwann cells acts as a master regulator of axonal regeneration after nerve injury by directly transcriptionally activating neurotrophic factor genes GDNF and Artemin (Ret ligands); Schwann cell-specific c-jun deletion impairs axonal regeneration and increases motoneuron death; genetic inactivation of the Ret receptor in neurons phenocopies the regeneration (but not survival) defect; recombinant GDNF and Artemin restore regeneration in c-jun-deficient animals. Schwann cell-specific c-jun conditional knockout mice, ChIP demonstrating direct c-Jun binding to GDNF and Artemin promoters, neuron-specific Ret knockout mice, recombinant GDNF/Artemin rescue experiments Journal of Cell Biology High 22753894
2013 c-Jun is specifically expressed in joint-forming interzone cells during embryonic limb development and is required for specification of joint cell fates; conditional c-jun deletion from limb bud mesenchyme causes failure of limb joint initiation and differentiation; c-Jun directly regulates Wnt16 and Wnt9a during early joint development, acting upstream of canonical Wnt activity in the joint interzone. Conditional c-jun knockout in limb mesenchyme (Prx1-Cre), transgenic reporter mice for Wnt9a enhancer, in silico AP-1 motif screen, ChIP-validated c-Jun binding to Wnt9a and Wnt16 regulatory elements Genes & Development High 23475960
2015 c-Jun acts as a barrier to iPSC reprogramming by activating mesenchymal-related genes and suppressing pluripotency genes; c-Jun drives mESCs toward the endoderm lineage and completely blocks the obligatory mesenchymal-to-epithelial transition required for reprogramming; inhibition of c-Jun by shRNA, dominant-negative c-Jun, or Jdp2 enhances reprogramming and can replace Oct4 among the Yamanaka factors. c-jun shRNA knockdown, dominant-negative c-Jun overexpression, iPSC reprogramming assays, mESC differentiation assays, transcriptome analysis Nature Cell Biology High 26098572
2002 c-Jun associates with the transcriptional corepressor Ski to enhance Ski–Smad2 association in the absence of TGF-β, maintaining active repression of Smad2-responsive genes; TGF-β signaling induces dissociation of c-Jun from Ski, relieving repression; JNK pathway activation suppresses TGF-β-induced c-Jun–Ski dissociation, providing a negative feedback mechanism. Co-immunoprecipitation of c-Jun, Ski, and Smad2, TGF-β stimulation, JNK pathway activation/inhibition Journal of Biological Chemistry Medium 12034730
2019 Overexpression of c-Jun in CAR T cells confers resistance to exhaustion by enhancing expansion potential, functional capacity, and anti-tumor potency; c-Jun overexpression reduces terminal differentiation and increases chromatin accessibility at AP-1 motifs, revealing that a functional deficiency of c-Jun mediates T cell exhaustion. Lentiviral c-Jun overexpression in human CAR T cells, five mouse tumor models in vivo, ATAC-seq chromatin accessibility, functional cytokine/expansion assays Nature High 31802004
2017 Ubiquitin-specific protease 6 (USP6) interacts with c-Jun and antagonizes its ubiquitination in an enzyme activity-dependent manner, thereby stabilizing c-Jun protein and upregulating c-Jun/AP-1 downstream signaling and cell invasion. DUB expression library screen, co-immunoprecipitation, ubiquitination assays, catalytic-dead USP6 mutant, invasion assays Molecular and Cellular Biology Medium 29061731
2016 The synaptic protein PRR7 translocates to the nucleus of hippocampal neurons following NMDA receptor activity and inhibits c-Jun ubiquitination by the E3 ligase SCF-FBW7, thereby increasing c-Jun-dependent transcriptional activity and promoting neuronal death; PRR7 knockdown attenuates NMDAR-mediated excitotoxicity in a c-Jun-dependent manner. PRR7 knockdown/overexpression, co-immunoprecipitation with FBW7, ubiquitination assays, microarray transcriptomics, primary neuronal excitotoxicity assays The EMBO Journal Medium 27458189
2010 p38γ MAPK acts both as an activator and a cofactor of c-Jun to transactivate MMP9; p38γ interacts with c-Jun (requiring p38γ phosphorylation and its C-terminus), increases c-Jun synthesis, and then is recruited by activated c-Jun as a cofactor into the MMP9 promoter to drive MMP9 transcription and cell invasion. Co-immunoprecipitation, ChIP of p38γ at MMP9 promoter, p38γ phosphorylation-dead and C-terminal mutants, MMP9 reporter assays, invasion assays Journal of Biological Chemistry Medium 20231272
2006 Nitric oxide disrupts the physical interaction between JNK1 and its substrate c-Jun through S-nitrosylation of JNK, inhibiting JNK-mediated c-Jun phosphorylation; this inhibition is reversible by thiol-reducing agents and is distinct from NO effects on SEK1–JNK interaction. In vitro kinase assay with NO donor (SNAP), dithiothreitol reversal, co-immunoprecipitation of JNK1 and c-Jun in intact cells, endogenous NO generation via interferon-γ, NOS inhibitor controls Biochemical and Biophysical Research Communications Medium 17054907
1996 c-Jun can interact directly with the DNA-binding/hinge region (CD regions) of the androgen receptor as shown in a modified yeast two-hybrid assay in COS cells; through this interaction, c-Jun supports androgen receptor-mediated transactivation in the absence of AP-1 DNA binding, and this effect is blocked by c-Fos. Modified yeast two-hybrid in COS cells, transient transfection reporter assays, time-course experiments, c-Fos competition Journal of Biological Chemistry Medium 8798722
2002 Bimolecular fluorescence complementation (BiFC) analysis revealed that regions outside the bZIP domains of c-Jun determine the subcellular locations of bZIP protein interactions in living cells, and that the subcellular sites of c-Jun interactions with other bZIP or Rel family proteins are regulated by cellular signaling; cross-family interactions between bZIP and Rel proteins (including c-Jun) affect subcellular localization and modulate transcriptional activation. Bimolecular fluorescence complementation (BiFC) in living cells, YFP fragment complementation, signaling perturbations Molecular Cell Medium 11983170
1993 NFATp, present in unstimulated T cells, forms a ternary complex with Jun and Fos homodimers or heterodimers on the IL-2 promoter; the DNA-binding domains of Fos and Jun are essential for NFATp–Fos–Jun–DNA complex formation; NFATp is a substrate for calcineurin phosphatase in vitro, linking the calcium/calcineurin pathway to AP-1 (c-Jun) co-complex assembly at cytokine gene promoters. Purified NFATp protein, in vitro calcineurin dephosphorylation assay, EMSA with recombinant Jun homodimers and Jun-Fos heterodimers, domain mutagenesis Nature High 8397339
1996 c-Jun stimulates polyomavirus large T antigen (LT)-mediated origin-dependent DNA unwinding ~5-fold by enhancing ATP-dependent LT binding to the replication origin ~7-fold; c-Jun interacts directly with LT (but not replication protein A) via its N-terminal region (distinct from the DNA-binding domain), revealing a DNA replication-promoting function of c-Jun independent of its transcriptional role. In vitro DNA unwinding assay with purified c-Jun and LT, in vitro replication assay, EMSA and DNase I footprinting of LT–origin binding, direct c-Jun–LT binding assay, N-terminal c-Jun deletion mutants The EMBO Journal Medium 8896457
2019 KDM4B, a Jumonji C-containing histone lysine demethylase, physically interacts with c-Jun at the IL-8, MMP1, and ITGAV promoters via its demethylation activity; KDM4B depletion reduces integrin αV expression and IL-8 production, and elevated KDM4B is associated with increased p-c-Jun in gastric cancer, establishing KDM4B as a coactivator of c-Jun-dependent transcription. Co-immunoprecipitation, ChIP of KDM4B and c-Jun at target promoters, KDM4B knockdown/overexpression, IL-8/MMP1 expression analysis Cell Death & Disease Medium 30683841
2013 TAp73α selectively induces expression of AP-1-motif-containing target genes in a manner dependent on endogenous c-Jun; TAp73β suppresses these same genes partly by downregulating c-Jun expression and impairing c-Jun recruitment to AP-1 sites, providing a molecular basis for functional differences between TAp73 isoforms in apoptosis regulation. ChIP-seq for TAp73α and TAp73β, RNA-seq, c-Jun ChIP at AP-1 sites, endogenous c-Jun knockdown Nucleic Acids Research Medium 21459846
2015 YAP/TAZ and AP-1 (c-Jun/c-Fos) co-occupy composite cis-regulatory enhancers genome-wide in breast cancer cells; YAP/TAZ, TEAD, and AP-1 form a physical complex that synergistically activates target genes controlling S-phase entry and mitosis; YAP/TAZ-induced oncogenic growth is severely blunted by AP-1 loss, and AP-1-promoted tumorigenesis is prevented in YAP/TAZ conditional knockout mice. ChIP-seq for YAP, TAZ, TEAD, and AP-1 components, co-immunoprecipitation of YAP/TAZ with c-Jun/c-Fos, conditional knockout mouse models, genetic AP-1 loss-of-function Nature Cell Biology High 26258633
2003 ATF3 physically associates with c-Jun and significantly enhances c-Jun-mediated neurite sprouting in neuronal-like cell lines; co-expression of ATF3 with c-Jun produces greater neurite outgrowth than c-Jun alone, suggesting that in axotomized neurons the ATF3–c-Jun heterodimer initiates an axonal regeneration program. Co-expression in neuronal cell lines, physical interaction assays (co-immunoprecipitation/pulldown), neurite outgrowth quantification Brain Research. Molecular Brain Research Medium 14667575
2013 BAG3 transcription is upregulated by c-Jun binding to the BAG3 promoter during normal growth conditions; in turn, BAG3 stabilizes JunD mRNA post-transcriptionally; serum starvation downregulates BAG3 via reduced c-Jun activity, contributing to growth inhibition, revealing a c-Jun→BAG3→JunD regulatory circuit. Promoter reporter assays with c-Jun overexpression/knockdown, BAG3 mRNA stability assays, JunD mRNA quantification after BAG3 modulation Biochimica et Biophysica Acta Low 24140207

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell 2995 8137421
1993 Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain. Genes & development 1747 8224842
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
1991 Phosphorylation of c-jun mediated by MAP kinases. Nature 1427 1922387
1987 Human proto-oncogene c-jun encodes a DNA binding protein with structural and functional properties of transcription factor AP-1. Science (New York, N.Y.) 1400 2825349
2002 Visualization of interactions among bZIP and Rel family proteins in living cells using bimolecular fluorescence complementation. Molecular cell 1266 11983170
1991 Cross-family dimerization of transcription factors Fos/Jun and ATF/CREB alters DNA binding specificity. Proceedings of the National Academy of Sciences of the United States of America 1244 1827203
2009 A census of human transcription factors: function, expression and evolution. Nature reviews. Genetics 1191 19274049
2004 Large-scale characterization of HeLa cell nuclear phosphoproteins. Proceedings of the National Academy of Sciences of the United States of America 1159 15302935
1996 Selective interaction of JNK protein kinase isoforms with transcription factors. The EMBO journal 1119 8654373
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
1988 Oncogene jun encodes a sequence-specific trans-activator similar to AP-1. Nature 1009 3347253
2012 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. Molecular cell 973 22681889
2015 Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth. Nature cell biology 946 26258633
2017 Impact of cytosine methylation on DNA binding specificities of human transcription factors. Science (New York, N.Y.) 934 28473536
1994 Ubiquitin-dependent c-Jun degradation in vivo is mediated by the delta domain. Cell 867 8087846
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2005 IL-13 signaling through the IL-13alpha2 receptor is involved in induction of TGF-beta1 production and fibrosis. Nature medicine 748 16327802
1993 The T-cell transcription factor NFATp is a substrate for calcineurin and interacts with Fos and Jun. Nature 715 8397339
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2019 c-Jun overexpression in CAR T cells induces exhaustion resistance. Nature 705 31802004
1998 Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-induced transcription. Nature 699 9732876
1995 Characterization of mechanisms involved in transrepression of NF-kappa B by activated glucocorticoid receptors. Molecular and cellular biology 695 7823959
1994 Activation of cAMP and mitogen responsive genes relies on a common nuclear factor. Nature 694 8028671
2017 Multi-omics analysis identifies ATF4 as a key regulator of the mitochondrial stress response in mammals. The Journal of cell biology 672 28566324
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1995 Crystal structure of the heterodimeric bZIP transcription factor c-Fos-c-Jun bound to DNA. Nature 636 7816143
1988 Transcriptional activation of c-jun during the G0/G1 transition in mouse fibroblasts. Nature 618 3136397
1991 Ha-Ras augments c-Jun activity and stimulates phosphorylation of its activation domain. Nature 611 1903181
2012 Constitutive AP-1 activity and EBV infection induce PD-L1 in Hodgkin lymphomas and posttransplant lymphoproliferative disorders: implications for targeted therapy. Clinical cancer research : an official journal of the American Association for Cancer Research 591 22271878
1994 JNK2 contains a specificity-determining region responsible for efficient c-Jun binding and phosphorylation. Genes & development 590 8001819
1997 MNK1, a new MAP kinase-activated protein kinase, isolated by a novel expression screening method for identifying protein kinase substrates. The EMBO journal 563 9155018
1988 Induction of protooncogene c-jun by serum growth factors. Proceedings of the National Academy of Sciences of the United States of America 491 3186736
1999 Control of cell cycle progression by c-Jun is p53 dependent. Genes & development 490 10072388
1993 c-jun is essential for normal mouse development and hepatogenesis. Nature 474 8371760
1992 Functional antagonism between c-Jun and MyoD proteins: a direct physical association. Cell 414 1310896
2003 Liver tumor development. c-Jun antagonizes the proapoptotic activity of p53. Cell 406 12553907
1997 Induction of apoptosis by the transcription factor c-Jun. The EMBO journal 403 9130714
1997 Reduced ubiquitin-dependent degradation of c-Jun after phosphorylation by MAP kinases. Science (New York, N.Y.) 402 8994040
2010 AP-1--The Jun proteins: Oncogenes or tumor suppressors in disguise? Cellular signalling 345 20060892
1990 Ionizing radiation regulates expression of the c-jun protooncogene. Proceedings of the National Academy of Sciences of the United States of America 326 2116003
2004 Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase. Science (New York, N.Y.) 317 14739464
1999 Smads bind directly to the Jun family of AP-1 transcription factors. Proceedings of the National Academy of Sciences of the United States of America 280 10220381
1996 Cellular transformation and malignancy induced by ras require c-jun. Molecular and cellular biology 249 8754851
2011 Targeting inflammation by modulating the Jun/AP-1 pathway. Annals of the rheumatic diseases 241 21339212
2003 A reinvestigation of the multisite phosphorylation of the transcription factor c-Jun. The EMBO journal 238 12881422
2011 c-Jun, at the crossroad of the signaling network. Protein & cell 237 22180088
2003 c-Jun regulates eyelid closure and skin tumor development through EGFR signaling. Developmental cell 232 12791272
1999 Functions of c-Jun in liver and heart development. The Journal of cell biology 222 10352021
2000 c-Jun and the transcriptional control of neuronal apoptosis. Biochemical pharmacology 221 11007936
2012 c-Jun in Schwann cells promotes axonal regeneration and motoneuron survival via paracrine signaling. The Journal of cell biology 219 22753894
2001 Cooperation between STAT3 and c-jun suppresses Fas transcription. Molecular cell 193 11463377
1998 Stress signals for apoptosis: ceramide and c-Jun kinase. Oncogene 191 9916990
2008 Probiotic Lactobacillus reuteri suppress proinflammatory cytokines via c-Jun. Inflammatory bowel diseases 180 18425802
1999 Interacting regions in Stat3 and c-Jun that participate in cooperative transcriptional activation. Molecular and cellular biology 177 10490649
1990 Estrogen stimulates transcription of c-jun protooncogene. Molecular endocrinology (Baltimore, Md.) 169 2126598
1995 Regulatory role of MEF2D in serum induction of the c-jun promoter. Molecular and cellular biology 165 7760790
1999 c-Jun is a JNK-independent coactivator of the PU.1 transcription factor. The Journal of biological chemistry 152 9988737
2013 AP-1/c-Jun transcription factors: regulation and function in malignant melanoma. European journal of cell biology 131 24315690
2004 Effect of deoxyribozymes targeting c-Jun on solid tumor growth and angiogenesis in rodents. Journal of the National Cancer Institute 131 15126605
1999 COP9 signalosome-directed c-Jun activation/stabilization is independent of JNK. The Journal of biological chemistry 124 10585392
2015 The oncogene c-Jun impedes somatic cell reprogramming. Nature cell biology 116 26098572
1995 Intramolecular signal transduction in c-Jun. The EMBO journal 116 7744008
2019 Oncofetal HLF transactivates c-Jun to promote hepatocellular carcinoma development and sorafenib resistance. Gut 109 31118247
2015 The transcription cofactor c-JUN mediates phenotype switching and BRAF inhibitor resistance in melanoma. Science signaling 109 26286024
1993 Activation of protooncogene c-jun by the X protein of hepatitis B virus. Virology 109 8390762
1998 Rb binds c-Jun and activates transcription. The EMBO journal 90 9545246
1996 c-Jun can mediate androgen receptor-induced transactivation. The Journal of biological chemistry 90 8798722
2008 Inhibition of transcriptional activity of c-JUN by SIRT1. Biochemical and biophysical research communications 87 18823944
2003 ATF3 enhances c-Jun-mediated neurite sprouting. Brain research. Molecular brain research 85 14667575
1990 Encounters with Fos and Jun on the road to AP-1. Seminars in cancer biology 85 2133107
1999 Lack of c-Jun activity increases survival to cisplatin. FEBS letters 83 10403393
1990 Transient induction of c-jun during hepatic regeneration. Hepatology (Baltimore, Md.) 80 2114348
2010 p38gamma MAPK cooperates with c-Jun in trans-activating matrix metalloproteinase 9. The Journal of biological chemistry 79 20231272
2016 miR-216b regulation of c-Jun mediates GADD153/CHOP-dependent apoptosis. Nature communications 78 27173017
1996 Activation of c-Jun-NH2-kinase by UV irradiation is dependent on p21ras. The Journal of biological chemistry 78 8798530
2014 Increased expression of c-Jun in nonalcoholic fatty liver disease. Laboratory investigation; a journal of technical methods and pathology 77 24492282
2001 A specific lysine in c-Jun is required for transcriptional repression by E1A and is acetylated by p300. The EMBO journal 76 11689449
1993 Interleukin 1 induction of the c-jun promoter. Proceedings of the National Academy of Sciences of the United States of America 74 8346217
2004 RANKing c-Jun in osteoclast development. The Journal of clinical investigation 72 15314680
2007 Nuclear import of c-Jun is mediated by multiple transport receptors. The Journal of biological chemistry 71 17652081
2006 Physical association with WWOX suppresses c-Jun transcriptional activity. Cancer research 71 17178850
1991 Positive regulation of jun/AP-1 by E1A. Molecular and cellular biology 67 1824713
2000 c-Jun promotes neurite outgrowth and survival in PC12 cells. Brain research. Molecular brain research 62 11072092
1989 Expression of c-jun protooncogene in human myelomonocytic cells. Blood 62 2477086
1991 Transcriptional control of c-jun by retinoic acid. Nucleic acids research 61 1851295
1996 Apoptosis and c-Jun in the thalamus of the rat following cortical infarction. Neuroreport 59 8730797
2015 Signalling in inflammatory skin disease by AP-1 (Fos/Jun). Clinical and experimental rheumatology 58 26458100
2012 DNAzyme targeting c-jun suppresses skin cancer growth. Science translational medicine 56 22723462
1995 ERM, a PEA3 subfamily of Ets transcription factors, can cooperate with c-Jun. The Journal of biological chemistry 55 7559555
2016 Pentraxin-2 suppresses c-Jun/AP-1 signaling to inhibit progressive fibrotic disease. JCI insight 54 27942582
2020 DGKA Provides Platinum Resistance in Ovarian Cancer Through Activation of c-JUN-WEE1 Signaling. Clinical cancer research : an official journal of the American Association for Cancer Research 53 32341033
2013 M-CSF cooperating with NFκB induces macrophage transformation from M1 to M2 by upregulating c-Jun. Cancer biology & therapy 53 24100343
1991 Expression of c-jun during macrophage differentiation of HL-60 cells. Blood 53 1904283
2011 Crosstalk between c-Jun and TAp73alpha/beta contributes to the apoptosis-survival balance. Nucleic acids research 47 21459846
2007 Stromally expressed c-Jun regulates proliferation of prostate epithelial cells. The American journal of pathology 47 17702894
1994 Sequence-specific impairment of learning by c-jun antisense oligonucleotides. Neuroreport 47 7948848
2017 Overexpression of c-Jun contributes to sorafenib resistance in human hepatoma cell lines. PloS one 45 28323861
2003 Transcriptional coactivation of c-Jun by the KSHV-encoded LANA. Blood 44 12969971
1994 Estrogen differentially affects c-jun expression in uterine tissue compartments. Endocrinology 42 8137749
2004 Deregulated repression of c-Jun provides a potential link to its role in tumorigenesis. Cell cycle (Georgetown, Tex.) 40 14712066
2014 Niclosamide enhances ROS-mediated cell death through c-Jun activation. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 38 24750999
2002 c-Jun associates with the oncoprotein Ski and suppresses Smad2 transcriptional activity. The Journal of biological chemistry 38 12034730
2021 BUB1B promotes extrahepatic cholangiocarcinoma progression via JNK/c-Jun pathways. Cell death & disease 36 33431813
2013 c-Jun is required for the specification of joint cell fates. Genes & development 36 23475960
2013 Overexpressed DNA polymerase iota regulated by JNK/c-Jun contributes to hypermutagenesis in bladder cancer. PloS one 36 23922701
2012 Transcriptional regulation of PES1 expression by c-Jun in colon cancer. PloS one 35 22860098
2002 Halofuginone inhibition of COL1A2 promoter activity via a c-Jun-dependent mechanism. Arthritis and rheumatism 35 12384935
2016 Synaptonuclear messenger PRR7 inhibits c-Jun ubiquitination and regulates NMDA-mediated excitotoxicity. The EMBO journal 34 27458189
1993 Multiple signal transduction pathways mediate c-Jun protein phosphorylation. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 34 8390855
2019 KDM4B is a coactivator of c-Jun and involved in gastric carcinogenesis. Cell death & disease 33 30683841
2019 Curcumin Inhibits ERK/c-Jun Expressions and Phosphorylation against Endometrial Carcinoma. BioMed research international 33 32083122
2014 Nerve injury-induced c-Jun activation in Schwann cells is JNK independent. BioMed research international 33 24877090
1992 Regulation of c-jun expression during induction of monocytic differentiation by okadaic acid. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 33 1419903
1996 c-Jun stimulates origin-dependent DNA unwinding by polyomavirus large Tantigen. The EMBO journal 32 8896457
2017 MALT1 promotes melanoma progression through JNK/c-Jun signaling. Oncogenesis 31 28759024
1991 Rapid induction of the c-jun protooncogene in the avian oviduct by the antiestrogen tamoxifen. Proceedings of the National Academy of Sciences of the United States of America 31 1704133
2017 Ubiquitin-Specific Protease USP6 Regulates the Stability of the c-Jun Protein. Molecular and cellular biology 30 29061731
2006 Nitric oxide inhibits an interaction between JNK1 and c-Jun through nitrosylation. Biochemical and biophysical research communications 30 17054907
2004 FOXO1 and c-jun transcription factors mRNA are modulated in endometriosis. Molecular human reproduction 30 15501904
2021 Higenamine alleviates allergic rhinitis by activating AKT1 and suppressing the EGFR/JAK2/c-JUN signaling. Phytomedicine : international journal of phytotherapy and phytopharmacology 29 33945919
2016 SPANXA suppresses EMT by inhibiting c-JUN/SNAI2 signaling in lung adenocarcinoma. Oncotarget 29 27323831
1998 Identification of domains of c-Jun mediating androgen receptor transactivation. Oncogene 29 9591784
2014 Potential role of proteasome on c-jun related signaling in hypercholesterolemia induced atherosclerosis. Redox biology 27 25009774
1992 SV40 large T inhibits myogenic differentiation partially through inducing c-jun. Journal of biochemistry 27 1331038
2016 MAGE-A1 promotes melanoma proliferation and migration through C-JUN activation. Biochemical and biophysical research communications 26 27045082
2013 BAG3 is upregulated by c-Jun and stabilizes JunD. Biochimica et biophysica acta 26 24140207