Affinage

Showing FOS — C-FOS is a alias.

FOS

Protein c-Fos · UniProt P01100

Length
380 aa
Mass
40.7 kDa
Annotated
2026-06-09
100 papers in source corpus 33 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

c-Fos is an immediate-early gene product that functions as a bZIP transcription factor, dimerizing with c-Jun, JunB, and JunD through its leucine zipper to form AP-1 complexes that bind AP-1 sites and regulate transcription (PMID:1945831); c-Jun heterodimers also remodel c-Fos nuclear mobility and redistribute it to the nuclear matrix independently of DNA binding (PMID:20053986). Its own expression is tightly controlled at multiple levels: transcription is governed by stimulus-specific enhancer subsets and SRE/STAT3/ELK1 inputs, with regulation occurring substantially at the elongation step where promoter-proximal polymerases must be converted to elongation-competent forms, and transactivation strength setting transcriptional burst kinetics (PMID:12600988, PMID:24981864, PMID:26595656, PMID:9671550); c-Fos additionally trans-represses its own promoter through the SRE via its leucine zipper, a function distinct from AP-1 transactivation (PMID:2513130). The mRNA is intrinsically unstable (~9 min half-life) through a 3'-UTR destabilizing element (PMID:3103102). c-Fos protein stability is set by a network of post-translational signals: MAPK/RSK and MEK5-ERK5 phosphorylation stabilize it and boost AP-1 activity, JNK serine phosphorylation protects it from PP2A-dependent proteasomal degradation, PRMT1-mediated arginine-287 methylation protects it from autophagic degradation, and dimerization with phosphorylated c-Jun targets it for degradation (PMID:8622865, PMID:12622723, PMID:15136564, PMID:37564212, PMID:1470918). Beyond nuclear transcription, dephosphorylated (tyrosine-10/30) c-Fos associates with the endoplasmic reticulum, where it directly binds and activates lipid-synthesis enzymes — CDP-diacylglycerol synthase, PtdIns 4-kinase IIα, and glucosylceramide synthase — to drive phospholipid and glycolipid synthesis in an AP-1-independent manner (PMID:11259365, PMID:17160021, PMID:18784083, PMID:21998197). In vivo, c-Fos is essential for osteoclast differentiation, acting downstream of MEF2C and upstream of NFATc1 (PMID:1465144, PMID:33424022, PMID:17189721), for neuronal excitability and survival via control of GluR6 and BDNF and for cocaine-induced neuronal plasticity (PMID:11925568, PMID:17182779), and for chondrocyte bioenergetic homeostasis by balancing pyruvate flux between glycolysis and the TCA cycle (PMID:37344157).

Mechanistic history

Synthesis pass · year-by-year structured walk · 32 steps
  1. 1986 Medium

    Established that c-fos is functionally required for cell proliferation rather than being a passive marker of mitogenic stimulation.

    Evidence Inducible antisense c-fos RNA in 3T3 cells with colony-formation and proliferation readouts

    PMID:3523478

    Open questions at the time
    • Antisense knockdown does not define which target genes mediate the proliferative effect
    • Single cell type
  2. 1987 High

    Defined the basis of c-fos transience by localizing an mRNA destabilizing element to the 3' UTR, explaining its immediate-early kinetics.

    Evidence mRNA half-life measurements with 3' UTR deletion/substitution mutants and cycloheximide treatment

    PMID:3103102

    Open questions at the time
    • Trans-acting decay factors not identified
    • Link between protein synthesis requirement and decay machinery unresolved
  3. 1988 Medium

    Identified the Fos C-terminus as the determinant of transcriptional autodownregulation, distinguishing oncogenic from normal Fos.

    Evidence Co-transfection of C-terminal Fos mutants with run-on transcription assays

    PMID:3149583

    Open questions at the time
    • Molecular mechanism of the C-terminal effect not defined
    • Single transient system
  4. 1989 High

    Separated c-Fos's repression of its own promoter from its activation function, showing autorepression requires dimerization but not DNA binding.

    Evidence Leucine zipper and DNA-binding mutants with c-fos promoter reporter assays

    PMID:2513130

    Open questions at the time
    • Identity of the partner protein mediating SRE-based repression unresolved
    • Endogenous chromosomal relevance not tested here
  5. 1991 Medium

    Defined c-Fos and c-Jun as calpain substrates, introducing proteolysis as a route to limit AP-1 factor lifetime.

    Evidence In vitro calpain digestion plus calpastatin manipulation in cells

    PMID:1908791

    Open questions at the time
    • Physiological significance of calpain cleavage of c-Fos in vivo not established
    • Cleavage sites not mapped
  6. 1991 High

    Established the AP-1 dimer logic by defining c-Fos as a Jun heterodimerization partner that activates, while Fra proteins suppress, Jun transactivation.

    Evidence In vitro dimerization, EMSA, and reporter assays with chimeric proteins

    PMID:1945831

    Open questions at the time
    • Genome-wide target spectrum not addressed
    • C-terminal regions mapped only functionally
  7. 1992 High

    Demonstrated in vivo that c-Fos is indispensable for osteoclast-mediated bone remodeling, anchoring its differentiation role in a defined lineage.

    Evidence Homozygous c-fos knockout mice with osteopetrosis phenotype

    PMID:1465144

    Open questions at the time
    • Downstream transcriptional targets in osteoclasts not identified at the time
    • Mechanism of lineage specificity unresolved
  8. 1992 High

    Linked c-Fos turnover to its dimerization partner's phosphorylation state, coupling signaling to AP-1 factor degradation.

    Evidence In vitro degradation and transient expression with phosphorylated vs. dephosphorylated c-Jun

    PMID:1470918

    Open questions at the time
    • Degradation pathway (proteasomal vs lysosomal) not yet assigned
    • Phospho-sites on Jun driving the effect not mapped
  9. 1993 Medium

    Showed MyoD represses c-fos via an SRE-overlapping site, mechanistically connecting muscle differentiation to shut-off of growth-responsive genes.

    Evidence Promoter mutagenesis, gel shift, and reporter assays in muscle cells

    PMID:8386804

    Open questions at the time
    • Endogenous chromosomal occupancy not shown
    • Generality beyond muscle cells untested
  10. 1996 High

    Mapped MAPK/RSK phosphorylation of c-Fos serines and tied it to increased stability and AP-1 activity during G1, defining a proliferative regulatory switch.

    Evidence In vitro kinase assays, Asp/Ala mutagenesis, half-life and AP-1 reporter assays

    PMID:8622865

    Open questions at the time
    • Degradation machinery acted upon by phosphorylation not defined here
    • In vivo relevance of specific sites not tested
  11. 1996 Medium

    Revealed a transcription-independent pro-apoptotic activity of c-Fos requiring p53 and blockable by Bcl-2, separating it from AP-1 transactivation.

    Evidence c-FosER chimera activation in p53-null and Bcl-2-expressing cells with cycloheximide

    PMID:8524298

    Open questions at the time
    • Molecular effector of the apoptotic activity not identified
    • Complex interpretation across multiple manipulations
  12. 1996 Medium

    Identified lysosomal selective degradation of c-Fos regulated by Jun dimerization, broadening the routes controlling c-Fos lifetime.

    Evidence Cell-free lysosome uptake assay and in vivo detection in leupeptin-treated rat liver lysosomes

    PMID:8706827

    Open questions at the time
    • Targeting signal directing c-Fos to lysosomes not defined
    • Relative contribution vs proteasomal/autophagic pathways unclear
  13. 1998 Medium

    Defined c-fos transcriptional control as primarily an elongation checkpoint, showing engaged polymerases terminate near the promoter until activation.

    Evidence Nucleotide-resolution nuclear run-on in intact cells

    PMID:9671550

    Open questions at the time
    • Factors driving the elongation switch not identified
    • Single-gene resolution limited to one system
  14. 1998 Medium

    Showed c-Fos can inhibit nuclear receptor signaling by sequestering c-Jun through its leucine zipper, a DNA-binding-independent repression.

    Evidence c-Fos truncation mutants with androgen-responsive promoter reporters

    PMID:9867253

    Open questions at the time
    • Endogenous AR target relevance not tested
    • Single reporter system
  15. 2001 Medium

    Discovered a cytoplasmic, AP-1-independent c-Fos function at the ER activating phospholipid synthesis, extending its role beyond transcription.

    Evidence 32P-lipid labeling, ER immunocytochemistry, and AP-1 nuclear-import blockade peptide

    PMID:11259365

    Open questions at the time
    • Direct enzyme targets not yet identified in this study
    • Mechanism of ER recruitment unresolved
  16. 2001 Medium

    Identified connexin43 as a direct AP-1 target of c-Fos/c-Jun, providing a concrete transcriptional output.

    Evidence Co-transfection with Cx43 promoter reporter and AP-1 site mutation

    PMID:12064606

    Open questions at the time
    • Single reporter assay without endogenous chromatin validation
    • Cell-type generality untested
  17. 2002 High

    Established a neuronal in vivo role for c-Fos in controlling excitability and survival through GluR6 and BDNF target regulation.

    Evidence Hippocampus-specific conditional c-fos knockout in a kainic acid seizure model

    PMID:11925568

    Open questions at the time
    • Direct vs indirect regulation of GluR6/BDNF not fully separated
    • AP-1 site occupancy at these targets not shown
  18. 2003 Medium

    Showed STAT3 and ELK1 cooperate on the endogenous c-fos promoter, integrating cytokine and MAPK inputs at the native chromosomal gene.

    Evidence ChIP on endogenous c-fos promoter plus reporter assays

    PMID:12600988

    Open questions at the time
    • Mechanism of STAT3-ELK1 additive cooperation not resolved
    • Single lab
  19. 2003 Medium

    Identified a distinct MEK5-ERK5 phosphorylation input stabilizing c-Fos and boosting its transactivation, separate from ERK1/2 sites.

    Evidence In vitro kinase assays with dominant-negative/constitutive MEK5/ERK5 and AP-1 reporters

    PMID:12622723

    Open questions at the time
    • Exact ERK5 phosphosites not mapped
    • In vivo significance untested
  20. 2004 High

    Resolved the degradation logic by showing JNK serine phosphorylation protects newly synthesized c-Fos from PP2A-triggered, ubiquitin-dependent proteasomal degradation.

    Evidence JNK/proteasome inhibitors, PP2A/PP2B treatment of immunoprecipitated c-Fos, ubiquitin IP in cardiomyocytes

    PMID:15136564

    Open questions at the time
    • E3 ligase mediating c-Fos ubiquitination not identified
    • Phosphosites protected by JNK not precisely mapped
  21. 2006 Medium

    Linked c-Fos tyrosine phosphorylation state to ER association, showing dephosphorylation of Tyr10/30 enables the lipid-synthesis activity.

    Evidence Tyrosine mutagenesis, subcellular fractionation, and 32P-lipid labeling

    PMID:17160021

    Open questions at the time
    • Kinase/phosphatase controlling Tyr10/30 not identified
    • Structural basis of ER membrane binding unknown
  22. 2006 High

    Demonstrated that a single c-Jun/c-Fos AP-1 dimer suffices for osteoclastogenesis and that c-Fos cannot be substituted by Fra1, defining functional specificity within AP-1.

    Evidence Synthetic single-chain AP-1 dimers rescuing osteoclastogenesis from c-Fos-null precursors

    PMID:17189721

    Open questions at the time
    • Molecular basis of c-Fos vs Fra1 transactivation difference not defined
    • Specific osteoclast target genes not enumerated
  23. 2006 High

    Extended the neuronal role of c-Fos to behavioral plasticity, showing D1-neuron c-Fos is required for cocaine-induced dendritic remodeling and gene expression changes.

    Evidence D1-neuron conditional c-fos knockout with behavioral, molecular, and dendritic readouts

    PMID:17182779

    Open questions at the time
    • Direct c-Fos target genes driving remodeling not pinned down
    • Circuit-level mechanism unresolved
  24. 2008 Medium

    Identified glucosylceramide synthase as a direct c-Fos-interacting enzyme activated to drive glycolipid synthesis, broadening the ER lipid-activation program.

    Evidence Glycolipid metabolic labeling, co-IP with tagged GlcCerS, and enzyme activity assays in PC12 cells

    PMID:18784083

    Open questions at the time
    • Mechanism of enzymatic activation not defined
    • Single cell type
  25. 2010 High

    Revealed that Jun partner identity controls c-Fos nuclear dynamics and matrix localization independently of DNA binding, adding a spatial layer to AP-1 regulation.

    Evidence FRAP, co-IP, fractionation, and DNA-binding mutants

    PMID:20053986

    Open questions at the time
    • Functional consequence of nuclear matrix redistribution for target gene output unclear
    • Matrix-anchoring partners not identified
  26. 2011 High

    Established direct physical and functional engagement of c-Fos with CDP-diacylglycerol synthase and PtdIns 4-kinase IIα via its N-terminus, mechanistically grounding the ER lipid-synthesis role.

    Evidence In vitro enzyme assays, co-IP, FRET, and N-terminal truncations

    PMID:21998197

    Open questions at the time
    • Structural model of c-Fos-enzyme complexes lacking
    • How nuclear vs ER c-Fos pools are partitioned unresolved
  27. 2015 High

    Connected transcription factor concentration and transactivation strength to the burst kinetics of c-fos transcription at single endogenous alleles.

    Evidence smFISH with synthetic TALE transcription factors and computational modeling

    PMID:24981864

    Open questions at the time
    • Endogenous TFs setting burst behavior not exhaustively defined
    • Link to chromatin state not addressed
  28. 2015 High

    Defined stimulus-specific combinatorial enhancer usage controlling c-fos induction in neurons, explaining context-dependent activation.

    Evidence Enhancer deletion/mutation, reporters, ChIP, and in vivo brain activation

    PMID:26595656

    Open questions at the time
    • Full TF complement at each enhancer not enumerated
    • Mechanism of enhancer-promoter selectivity unresolved
  29. 2021 High

    Placed c-FOS upstream in osteoclastogenesis as the MEF2C-induced activator of NFATc1, completing a defined RANKL-responsive transcriptional cascade.

    Evidence ChIP of MEF2C at FOS, conditional Mef2c knockout mice, expression manipulation, and transcriptomics

    PMID:33424022

    Open questions at the time
    • Direct c-FOS occupancy at Nfatc1 not detailed here
    • Co-factors at FOS regulatory regions not fully mapped
  30. 2021 Medium

    Showed c-FOS drives a reversible basal-to-squamous carcinoma transition by remodeling AP-1 element accessibility, linking it to malignant cell-state plasticity.

    Evidence Inducible c-FOS, ATAC-seq, EGFR inhibition, mouse models, and patient transcriptomics

    PMID:34610301

    Open questions at the time
    • Specific AP-1 elements driving transition not enumerated
    • Single lab
  31. 2023 High

    Defined c-Fos as a metabolic regulator in chondrocytes balancing pyruvate flux, with loss exacerbating osteoarthritis and rescuable by Pdk inhibition.

    Evidence Cartilage-specific c-fos knockout, DMM OA model, in situ enzyme assays, RNA-seq, and DCA rescue

    PMID:37344157

    Open questions at the time
    • Direct transcriptional targets controlling Pdh/Ldh/HIF-1α axis not pinpointed
    • Whether the effect is AP-1-dependent not resolved
  32. 2023 Medium

    Identified PRMT1-mediated arginine-287 methylation as a stabilizing modification protecting c-Fos from autophagic degradation and enhancing AP-1 activity.

    Evidence Co-IP, mass spectrometry of methylation sites, PRMT1 knockdown, autophagy inhibition, and AP-1 reporters

    PMID:37564212

    Open questions at the time
    • Full R287 mutagenesis validation not described
    • Autophagy receptor recognizing unmethylated c-Fos unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How nuclear AP-1 transcription-factor c-Fos and the cytoplasmic ER-bound lipid-activating c-Fos pools are partitioned, coordinated, and integrated within a single cell remains unresolved.
  • No structural model linking the two activities
  • Signals dictating nuclear vs ER fate not fully defined
  • Stoichiometry between pools unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0098772 molecular function regulator activity 3 GO:0003677 DNA binding 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0005783 endoplasmic reticulum 4 GO:0005634 nucleus 3
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1266738 Developmental Biology 4 R-HSA-1430728 Metabolism 4 R-HSA-162582 Signal Transduction 4
Partners
CDS1JUNJUNBJUNDPI4K2APRMT1STAT3UGCG
Complex memberships
AP-1

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 c-Fos is essential for osteoclast and bone development in vivo; c-fos knockout mice develop osteopetrosis with deficiencies in bone remodeling and altered haematopoiesis, defining c-Fos as a required transcription factor for specific cellular differentiation compartments. Gene targeting in embryonic stem cells; homozygous knockout mice phenotypic analysis Nature High 1465144
1986 c-fos mRNA is required for normal cell division in 3T3 cells; inducible antisense RNA complementary to c-fos mRNA decreased colony formation and inhibited cell proliferation. Antisense RNA gene transfer with inducible MMTV promoter; colony formation and proliferation assays Proceedings of the National Academy of Sciences of the United States of America Medium 3523478
1987 c-fos mRNA undergoes rapid post-transcriptional degradation with a half-life of ~9 minutes, dependent on a destabilizing element in its 3' untranslated region; stabilization requires continued protein synthesis (cycloheximide blocks degradation). mRNA half-life measurements with 3' deletion/substitution mutants; cycloheximide treatment; Northern blot Nucleic acids research High 3103102
1989 c-Fos protein trans-represses its own promoter (c-fos autoregulation) through the serum response element (SRE); this trans-repression requires the leucine zipper (protein complex formation) but not AP-1/ATF sites, and is distinct from trans-activation. Transient transfection with Fos leucine zipper and DNA-binding mutants; reporter gene assays with c-fos promoter deletions Cell High 2513130
1988 Mutations at the C-terminus of Fos protein (of the type found in virally-transduced transforming Fos variants) prevent rapid down-regulation of c-fos transcription following serum stimulation and act dominantly in trans to prevent down-regulation of a co-transfected c-fos gene. Transient co-transfection with C-terminal Fos mutants; run-on transcription assays The EMBO journal Medium 3149583
1991 c-Fos forms stable heterodimers with c-Jun, JunB, and JunD through their leucine zipper domains; heterodimers bind AP-1 sites and regulate transcription. c-Fos stimulates transcriptional activity of c-Jun heterodimers, whereas Fra-2 (and Fra-1) suppress c-Jun transactivation, with differences mapping to C-terminal regions. In vitro dimerization assays; gel shift/EMSA; transient transfection reporter assays; chimeric protein analysis Nucleic acids research High 1945831
1992 c-Fos stability is regulated by dimerization with phosphorylated c-Jun: phosphorylated c-Jun targets c-Fos for degradation in a signal-dependent manner, whereas phorbol ester-induced (dephosphorylated) c-Jun stabilizes c-Fos. v-Fos is not susceptible to c-Jun-targeted degradation. Transient expression assays; in vitro degradation experiments with phosphorylated vs. unphosphorylated c-Jun Science High 1470918
1996 c-Fos is phosphorylated by MAP kinase and RSK at serines 362 and 374 (rat) in vivo during early G1; phosphorylation-mimicking mutations (S→D) increase c-Fos stability and AP-1 transactivation activity, whereas alanine substitutions reduce stability, indicating phosphorylation supports proliferative responses. In vitro kinase assays with MAP kinase and RSK; site-directed mutagenesis (Asp/Ala substitutions); AP-1 reporter assays; protein half-life measurements Oncogene High 8622865
1996 c-Fos protein can induce apoptosis in preneoplastic cells in a manner that does not require new protein synthesis, does not involve its transcriptional activation activity (v-Fos which is transcriptionally active but lacks repression activity fails to induce apoptosis), and is blocked by Bcl-2 overexpression and requires p53. Chimeric c-FosER fusion protein activation; cycloheximide treatment; Bcl-2 co-expression; p53-null cell lines and HPV E6-mediated p53 knockdown; apoptosis assays Molecular and cellular biology Medium 8524298
2001 c-Fos associates with the endoplasmic reticulum and activates phospholipid metabolism by an AP-1-independent cytoplasmic activity; two waves of c-Fos expression stimulate sequential synthesis of signaling polyphosphoinositides then membrane-biogenesis phospholipids; a peptide blocking AP-1 nuclear import does not affect this lipid activation. 32P-orthophosphate incorporation into lipid fractions; immunocytochemistry showing ER localization; AP-1 nuclear import blockade peptide; timing of c-Fos expression waves FASEB journal Medium 11259365
2006 c-Fos/ER association and cytoplasmic phospholipid synthesis activation are regulated by the phosphorylation state of c-Fos N-terminal tyrosine residues 10 and 30: tyrosine-phosphorylated c-Fos is not ER-membrane bound, while dephosphorylated c-Fos associates with the ER and promotes phospholipid synthesis. Site-directed mutagenesis of tyrosine residues; subcellular fractionation; 32P-lipid labeling; phosphotyrosine immunoblotting; cell proliferation assays Oncogene Medium 17160021
2008 c-Fos activates glucosylceramide synthase (GlcCerS) and glycolipid synthesis in PC12 cells; c-Fos physically interacts with GlcCerS as demonstrated by co-immunoprecipitation, and activates its enzymatic activity without affecting downstream glycolipid synthesis enzymes. Metabolic labeling of glycolipids; co-immunoprecipitation of c-Fos with V5-tagged GlcCerS; enzymatic activity assays for GlcCerS and downstream enzymes The Journal of biological chemistry Medium 18784083
2011 c-Fos physically interacts with and activates CDP-diacylglycerol synthase and phosphatidylinositol 4-kinase IIα (but not PtdIns synthase or PtdIns 4-kinase IIβ) via its N-terminal domain, stimulating polyphosphoinositide synthesis; interaction confirmed by co-immunoprecipitation and FRET. In vitro enzyme activity assays; co-immunoprecipitation; FRET (fluorescence resonance energy transfer); N-terminal domain truncation constructs Molecular biology of the cell High 21998197
1991 c-Fos and c-Jun are substrates for calpain (calcium-dependent neutral protease) in vitro; calpain efficiently digests both proteins, and c-Jun calpain activity can be modified in vivo by manipulating calpastatin (endogenous calpain inhibitor) levels. In vitro calpain digestion assay; calpastatin overexpression/manipulation in cultured cells FEBS letters Medium 1908791
1996 Lysosomes selectively take up and degrade c-Fos in a cell-free assay; lysosomal uptake of c-Fos is regulated by dimerization with differentially phosphorylated c-Jun, and c-Fos is immunologically detected in leupeptin-treated rat liver lysosomes in vivo, while v-Fos escapes this regulation. Cell-free lysosome uptake/degradation assay; immunological detection of c-Fos in purified lysosomes from leupeptin-treated rats FEBS letters Medium 8706827
2004 JNK-mediated phosphorylation of newly synthesized c-Fos at serine residues protects c-Fos from proteasomal degradation in cardiomyocytes; dephosphorylation by PP2A (but not PP2B/calcineurin) triggers ubiquitin-dependent proteasomal degradation of c-Fos. Pharmacological JNK inhibitor; proteasome inhibitors (MG132, PI-1); PP2A and PP2B phosphatase treatment of immunoprecipitated c-Fos; phosphoserine/threonine immunoblotting; ubiquitin immunoprecipitation The Journal of biological chemistry High 15136564
1993 MyoD binds a site overlapping the serum response element (SRE) in the c-fos promoter and acts as a negative transcriptional regulator of c-fos, blocking serum responsiveness; this identifies a mechanism by which MyoD can inhibit growth-responsive gene expression during muscle differentiation. Promoter deletion/mutation analysis; gel shift assays identifying MyoD binding site; transient transfection reporter assays in muscle cells Nature Medium 8386804
2002 c-Fos regulates neuronal excitability and survival by controlling expression of the kainic acid receptor GluR6 and BDNF; hippocampus-specific c-fos knockout mice show increased kainic acid-induced seizures, neuronal excitability, and neuronal death. Conditional hippocampus-specific c-fos knockout mice; kainic acid-induced seizure model; in vivo and in vitro gene expression analysis of GluR6 and BDNF Nature genetics High 11925568
2006 c-Fos produced in D1 receptor-expressing neurons regulates acquisition and extinction of cocaine-induced persistent changes; c-Fos-deficient neurons show altered expression of transcription factors, neurotransmitter receptors, and intracellular signaling molecules, and blunted dendritic remodeling of medium spiny neurons after repeated cocaine. Neuron-specific (D1 receptor-expressing) c-fos conditional knockout mice; cocaine sensitization and conditioned place preference behavioral tests; Western blot and immunohistochemistry for downstream targets; dendritic morphology analysis The Journal of neuroscience High 17182779
2003 STAT3 (but not STAT1) accumulates on the chromosomal c-fos promoter and independently boosts transcription; STAT3 cooperates with resident nuclear proteins (ELK1) activated by MAPK pathways to produce additive transcriptional increases, acting on the native chromosomal gene. Chromatin immunoprecipitation (ChIP) on endogenous c-fos promoter; transient transfection with STAT3/STAT1; luciferase reporter assays The Journal of biological chemistry Medium 12600988
2003 The MEK5-ERK5 pathway phosphorylates and stabilizes c-Fos at sites distinct from those phosphorylated by ERK1/2, and the C-terminal half of ERK5 is required for maximal activation of c-Fos transactivation activity. In vitro kinase assays; dominant-negative and constitutively active MEK5/ERK5 constructs; c-Fos stability/phosphorylation assays; AP-1 reporter assays Genes to cells Medium 12622723
2010 c-Fos intranuclear mobility and distribution are differentially regulated by its Jun dimerization partners: heterodimerization with c-Jun causes dramatic reduction in c-Fos nuclear mobility and redistribution to the nuclear matrix independently of AP-1/CRE DNA binding, while dimerization with JunB does not affect c-Fos mobility but alters its intranuclear distribution differently. FRAP (fluorescence recovery after photobleaching); co-immunoprecipitation; subcellular fractionation; fluorescent protein fusions; genetic mutants lacking DNA-binding capacity The Journal of biological chemistry High 20053986
1998 c-Fos dimerization with c-Jun (through the leucine zipper) represses c-Jun-mediated enhancement of androgen receptor transactivation; the bZIP leucine zipper (dimerization) domain of c-Fos is required and sufficient for this inhibition, while DNA binding is dispensable. Transient transfection reporter assays with c-Fos truncation mutants; hKLK2 promoter-luciferase constructs Endocrine Medium 9867253
2001 c-Fos and c-Jun co-activate connexin43 (Cx43) promoter through an AP-1 site; mutation of the AP-1 site reduces this responsiveness, identifying Cx43 as a direct transcriptional target of c-Fos/c-Jun AP-1 complexes in myometrial cells. Transient co-transfection with c-Fos and c-Jun expression vectors; Cx43 promoter-luciferase reporter; AP-1 site mutation Cell communication & adhesion Medium 12064606
2013 TLR7 negatively regulates dendrite outgrowth through a Myd88-c-Fos-IL-6 signaling pathway; TLR7 activation induces IL-6 through Myd88, and c-Fos is required for this pathway as shown by genetic knockouts of Myd88 and IL-6. In vitro neuronal cultures; in utero electroporation; Myd88-/-, IL-6-/-, TNFα-/- neurons; TLR7 agonist treatments; dendrite morphology quantification The Journal of neuroscience Medium 23843519
2021 MEF2C directly binds FOS regulatory regions to induce c-FOS expression, which then activates NFATc1 and drives osteoclastogenesis; MEF2C-mediated c-FOS induction is required for RANKL-induced osteoclast differentiation. ChIP assay showing MEF2C binding to FOS regulatory regions; MEF2C ectopic expression and knockdown; conditional Mef2c knockout mice; osteoclastogenesis assays; transcriptomic analysis Bone research High 33424022
2006 A single c-Jun/c-Fos AP-1 dimer is sufficient for osteoclast differentiation from c-Fos-deficient hematopoietic precursors; c-Fos heterodimerized with any Jun protein (including JNK-phosphorylation-site mutant c-Jun) rescues osteoclastogenesis, but Fra1 with any Jun protein cannot rescue, suggesting c-Fos has broader AP-1 site transactivation capability required for osteoclast differentiation. Synthetic single-chain AP-1 dimers (tethered via linker); rescue of osteoclastogenesis from c-Fos-deficient precursors; transient transfection AP-1 reporter assays Bone High 17189721
2023 c-Fos modulates cellular bioenergetics in chondrocytes by balancing pyruvate flux between anaerobic glycolysis and the TCA cycle; cartilage-specific c-Fos knockout mice show decreased pyruvate dehydrogenase (Pdh) activity, elevated lactate dehydrogenase (Ldh) activity, and elevated HIF-1α/Pdk1/Ldha expression, with exacerbated OA. DCA (Pdk inhibitor) treatment rescues these metabolic and structural defects. Cartilage-specific conditional c-fos knockout (c-FosΔCh); DMM OA model; RNA-seq; in situ metabolic enzyme activity assays for Pdh and Ldh; DCA pharmacological rescue Annals of the rheumatic diseases High 37344157
2023 PRMT1 directly interacts with c-Fos and methylates it at arginine 287 (mono- and dimethylation), protecting c-Fos from autophagic degradation and enhancing AP-1 transcriptional activity; PRMT1 knockdown decreases c-Fos protein levels, and R287 methylation promotes c-Fos protein stabilization. Co-immunoprecipitation; mass spectrometry identification of methylation sites; PRMT1 knockdown; autophagy inhibition experiments; AP-1 reporter assays International journal of biological sciences Medium 37564212
2015 During MAPK induction, transcription factor concentration modulates the burst frequency of c-Fos transcription; the polymerase initiation frequency is linked to transactivation domain strength, and burst duration is linked to TF lifetime on the promoter, as shown using synthetic TALE-based TFs. Single-molecule FISH (smFISH) with computational modeling; synthetic TALE transcription factors targeting c-Fos promoter; quantification at individual endogenous alleles Cell reports High 24981864
2015 Multiple enhancers surrounding the c-fos gene are required for robust c-fos response to various stimuli; membrane depolarization, BDNF, and forskolin activate distinct subsets of enhancers to induce c-fos transcription in neurons, with different key transcription factors required depending on the type of stimulation. Enhancer deletion/mutation analysis; luciferase reporter assays; ChIP; neuronal stimulation with defined stimuli; in vivo brain activation Nature neuroscience High 26595656
2021 c-FOS drives basal to squamous cell carcinoma transition (BST) by regulating the accessibility of distinct AP-1 regulatory elements; c-FOS-mediated BST is reversible, and EGFR pathway blockade after c-FOS induction reverts BST in vitro and prevents BST features in mouse models and human tumors. Inducible c-FOS expression systems; ATAC-seq/chromatin accessibility assays; EGFR inhibitor treatment; mouse models; patient single-cell and bulk transcriptomics Cell reports Medium 34610301
1998 RNA polymerases are constitutively engaged at the c-fos promoter-proximal region in the absence of activation signals but terminate close to the promoter; activation of c-fos expression results primarily from assembly of elongation-competent RNA polymerases that can transcribe the complete gene, establishing transcription elongation as a key regulatory step. Nuclear run-on transcription analysis at nucleotide resolution in intact cells; promoter occupancy and chromatin conformation analysis Journal of molecular biology Medium 9671550

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1989 The use of c-fos as a metabolic marker in neuronal pathway tracing. Journal of neuroscience methods 1274 2507830
1992 Bone and haematopoietic defects in mice lacking c-fos. Nature 786 1465144
1996 Activation of c-fos in the brain. Progress in neurobiology 607 8971979
1989 Expression of c-Fos immunoreactivity in transmitter-characterized neurons after stress. Proceedings of the National Academy of Sciences of the United States of America 512 2512584
1986 Inducible production of c-fos antisense RNA inhibits 3T3 cell proliferation. Proceedings of the National Academy of Sciences of the United States of America 511 3523478
1991 c-fos mRNA, Fos, and Fos-related antigen induction by hypertonic saline and stress. The Journal of neuroscience : the official journal of the Society for Neuroscience 491 1908006
1984 Expression of the c-fos gene and of an fos-related gene is stimulated by platelet-derived growth factor. Science (New York, N.Y.) 460 6093261
1998 Using c-fos as a neural marker of pain. Brain research bulletin 421 9434195
1985 Induction of c-fos during myelomonocytic differentiation and macrophage proliferation. Nature 363 3887183
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1996 Induction of apoptosis by c-Fos protein. Molecular and cellular biology 228 8524298
1988 Estrogen regulation of c-fos messenger ribonucleic acid. Molecular endocrinology (Baltimore, Md.) 220 3141795
1986 c-fos expression is neither sufficient nor obligatory for differentiation of monomyelocytes to macrophages. Cell 220 3085953
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2014 Transcription factors modulate c-Fos transcriptional bursts. Cell reports 219 24981864
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1989 trans-repression of the mouse c-fos promoter: a novel mechanism of Fos-mediated trans-regulation. Cell 203 2513130
1993 Persistent induction of c-fos and c-jun expression by asbestos. Proceedings of the National Academy of Sciences of the United States of America 175 8386370
1998 Forebrain expression of c-fos due to active maternal behaviour in lactating rats. Neuroscience 168 9483519
1991 Degradation of transcription factors, c-Jun and c-Fos, by calpain. FEBS letters 157 1908791
1996 Phosphorylation of c-Fos at the C-terminus enhances its transforming activity. Oncogene 146 8622865
2014 Using c-fos to study neuronal ensembles in corticostriatal circuitry of addiction. Brain research 142 25446457
1988 Morphine activation of c-fos expression in rat brain. Biochemical and biophysical research communications 142 3144275
1986 c-myc and c-fos expression in differentiating mouse primary keratinocytes. The EMBO journal 134 2431900
2006 c-Fos facilitates the acquisition and extinction of cocaine-induced persistent changes. The Journal of neuroscience : the official journal of the Society for Neuroscience 122 17182779
1987 Modulation of c-fos gene transcription by negative and positive cellular factors. Nature 121 3561489
1989 Induction of c-fos and TIS genes in cultured rat astrocytes by neurotransmitters. Journal of neuroscience research 120 2572704
1986 Barium modulates c-fos expression and post-translational modification. Proceedings of the National Academy of Sciences of the United States of America 119 2430291
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2003 c-Fos expression in hypothalamic nuclei of food-entrained rats. American journal of physiology. Regulatory, integrative and comparative physiology 109 12933360
1992 Targeted degradation of c-Fos, but not v-Fos, by a phosphorylation-dependent signal on c-Jun. Science (New York, N.Y.) 106 1470918
1988 c-fos expression interferes with thymus development in transgenic mice. Cell 99 3133119
1988 Fos C-terminal mutations block down-regulation of c-fos transcription following serum stimulation. The EMBO journal 99 3149583
1993 Repression of c-fos promoter by MyoD on muscle cell differentiation. Nature 98 8386804
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1993 c-fos expression in vasopressin and oxytocin neurons reveals functional heterogeneity within magnocellular neurons. Neuroendocrinology 88 8321410
2005 Roles for NF-kappaB and c-Fos in osteoclasts. Journal of bone and mineral metabolism 84 15984408
2003 Independent and cooperative activation of chromosomal c-fos promoter by STAT3. The Journal of biological chemistry 77 12600988
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1990 Insulin's regulation of c-fos gene transcription in hepatoma cells. The Journal of biological chemistry 67 2114401
1988 Proto-oncogene c-fos induction in rat hippocampus. Brain research 67 3382942
2000 Tactile experience induces c-fos expression in rat barrel cortex. Learning & memory (Cold Spring Harbor, N.Y.) 66 10753978
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1987 The chicken c-fos gene: cloning and nucleotide sequence analysis. Journal of virology 64 3316710
2013 TLR7 negatively regulates dendrite outgrowth through the Myd88-c-Fos-IL-6 pathway. The Journal of neuroscience : the official journal of the Society for Neuroscience 63 23843519
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2022 A c-Fos activation map in nitroglycerin/levcromakalim-induced models of migraine. The journal of headache and pain 43 36180824
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1993 UVB-induced DNA breaks interfere with transcriptional induction of c-fos. Molecular and cellular biology 40 8413289
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1989 Elevated c-fos expression inhibits differentiation of L6 rat myoblasts. Journal of cellular physiology 35 2469685
2014 Up-regulation of c-Fos associated with neuronal apoptosis following intracerebral hemorrhage. Cellular and molecular neurobiology 34 25354492
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1996 Expression of c-fos gene inhibits proteoglycan synthesis in transfected chondrocyte. FEBS letters 29 8601460
1988 Enhancement of c-fos expression is associated with activated macrophages. Oncogene 29 3131720
2017 MiR-30a attenuates osteoclastogenesis via targeting DC-STAMP-c-Fos-NFATc1 signaling. American journal of translational research 28 29312525
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1998 c-Fos dimerization with c-Jun represses c-Jun enhancement of androgen receptor transactivation. Endocrine 28 9867253
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