Affinage

ATF1

Cyclic AMP-dependent transcription factor ATF-1 · UniProt P18846

Length
271 aa
Mass
29.2 kDa
Annotated
2026-06-09
100 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATF1 is a bZIP transcription factor of the CREB/ATF family that binds CRE/ATF DNA elements as homodimers or as heterodimers with CREB and drives cAMP- and stress-responsive transcription (PMID:1655749). Its activity is gated by phosphorylation at Ser63, which induces a conformational change, enhances DNA binding by both homo- and heterodimers, and stimulates transcription from ATF/CRE promoters (PMID:8414969, PMID:9016641); this phosphorylation is executed by multiple kinases converging from distinct signaling inputs — MAPKAP kinase-2 downstream of p38 upon FGF/stress (PMID:8887554), MSK1/MSK2 in response to stress and mitogens (PMID:11909979), MSK1 downstream of ERK1/2 for EGF-induced c-jun activation (PMID:12414794), and RSK2, which couples ATF1 to Ras-mediated neoplastic transformation (PMID:21098035). Through these inputs ATF1 controls a broad target program: it activates c-jun (PMID:12414794), NOX1 in vascular smooth muscle (PMID:15491278), hypoxia-induced UCP3 (PMID:18579531), and TGF-β2 via recruitment of p300/CBP coactivators (PMID:10567368), and it represses the ferritin H antioxidant-response element, an activity antagonized by PIAS3 (PMID:17565989). ATF1 is integral to cellular stress and differentiation responses, partnering with HSF1 to recruit BRG1 and p300/CBP to the HSP70 promoter during heat shock (PMID:25312646), and acting with CREB as a required factor in cAMP-dependent neuronal differentiation (PMID:9489722) and adipogenesis (PMID:17071615). ATF1 also interacts physically with BRCA1, which stimulates CRE-dependent transcription (PMID:10945975). In cancer, the t(12;22) translocation fuses the EWS N-terminal activation domain to the ATF1 bZIP domain, producing EWS/ATF1, a constitutive transcriptional activator that causes clear cell sarcoma (PMID:8401579, PMID:7753552); EWS/ATF1 DNA-binding is required for tumor cell viability (PMID:10574952), retargets ATF1 to novel distal enhancers and rewires 3D chromatin architecture to establish oncogenic gene programs (PMID:35477713, PMID:31488818), and induces FOS to drive proliferation (PMID:23281395).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 1991 High

    Established ATF1 as a CRE-binding bZIP factor that dimerizes with CREB and mediates cAMP/PKA-responsive transcription, defining its founding identity.

    Evidence cDNA sequencing, in vitro dimerization, EMSA, and PKA-driven reporter assays

    PMID:1655749

    Open questions at the time
    • Endogenous target genes not yet identified
    • In vivo physiological role unaddressed
  2. 1993 High

    Identified the t(12;22) EWS/ATF1 fusion linking the ATF1 bZIP domain to the EWS activation domain in clear cell sarcoma, opening the oncogenic dimension of ATF1 biology.

    Evidence RT-PCR and cDNA cloning/sequencing of fusion transcripts from tumor specimens

    PMID:8401579

    Open questions at the time
    • Transcriptional consequences of the fusion not yet defined
    • Cell of origin unknown
  3. 1993 Medium

    Defined critical serine residues whose phosphorylation induces a conformational change modulated by dimerization and DNA binding, with one serine unique to ATF1, hinting at a specialized activation mode.

    Evidence In vitro phosphorylation, serine mutagenesis, and DNA binding stability assays

    PMID:8414969

    Open questions at the time
    • No cellular validation in this study
    • Responsible kinase not identified
  4. 1995 Medium

    Showed EWS/ATF1 acts as a strong constitutive activator (and selective repressor) of ATF1-binding promoters, mechanistically distinguishing the fusion from wild-type ATF1.

    Evidence Transient transfection reporter assays in JEG3 and MMSP cell lines

    PMID:7753552

    Open questions at the time
    • Endogenous fusion target genes not mapped
    • Correlative promoter activity, not direct binding
  5. 1996 High

    Placed ATF1 phosphorylation downstream of the p38 MAPK → MAPKAP kinase-2 cascade in response to FGF and cellular stress, establishing a stress-signaling input.

    Evidence In vitro kinase assay, dominant-negative Ras, SB203580 inhibition, Gal4 reporter assays

    PMID:8887554

    Open questions at the time
    • Direct ATF1 (vs CREB) phosphorylation site detail limited
    • Downstream target genes not enumerated
  6. 1997 Medium

    Demonstrated that Ser63 phosphorylation enhances ATF1 DNA binding and stimulates transcription, identifying the key activating modification.

    Evidence In vitro dephosphorylation, EMSA, and in vitro transcription from the Na,K-ATPase α1 promoter

    PMID:9016641

    Open questions at the time
    • Direct Ser63 mutagenesis not reported here
    • Cellular kinase responsible not assigned
  7. 1997 Medium

    Extended ATF1's promoter repertoire to viral (EBV BZLF1 ZII) and cellular (histone H4) targets and showed isoform-specific subnuclear partitioning, broadening its functional context.

    Evidence EMSA, UV cross-linking, IP, subnuclear fractionation, and reporter assays with deletion/mutagenesis

    PMID:9018131 PMID:9398163

    Open questions at the time
    • Functional significance of isoform partitioning unclear
    • Single-lab promoter studies
  8. 1998 Medium

    Dissected the EWS activation domain of the fusion, showing transactivation is dimerization-independent with determinants dispersed across the EAD acting synergistically.

    Evidence Mutational analysis with reporter assays in mammalian and yeast systems

    PMID:9569031

    Open questions at the time
    • Coactivators recruited by the EAD not identified
    • Endogenous targets untested
  9. 1999 Medium

    Demonstrated that EWS/ATF1 DNA-binding activity is essential for clear cell sarcoma tumor cell survival, validating it as a therapeutic dependency.

    Evidence Intracellular anti-ATF1 scFv delivery into SU-CCS-1 cells with CRE reporter and apoptosis assays

    PMID:10574952

    Open questions at the time
    • Mechanism of cell death downstream of fusion not defined
    • Single cell line
  10. 1999 Medium

    Linked ATF1/CREB and p300/CBP coactivation to TGF-β2 transcription, tying ATF1 phosphorylation to coactivator-dependent gene induction during differentiation.

    Evidence Transient transfection, kinase co-expression, reporter assays, phospho-CREB western blot

    PMID:10567368

    Open questions at the time
    • Direct ATF1 occupancy at the TGF-β2 promoter not shown by ChIP
    • Relative ATF1 vs CREB contribution unresolved
  11. 2000 High

    Identified BRCA1 as a direct physical partner of ATF1 that stimulates CRE-dependent transcription, connecting ATF1 to a tumor-suppressor protein.

    Evidence Yeast two-hybrid, in vitro pull-down, co-IP in human cells, and CRE/TNF-α reporter assays

    PMID:10945975

    Open questions at the time
    • Physiological context of the interaction unclear
    • Effect on endogenous BRCA1 target genes untested
  12. 2001 Medium

    Refined fusion regulation by showing EWS Ser266 phosphorylation and conserved EAD tyrosines in hexapeptide repeats are required for EWS/ATF1 transactivation and compartmentalization.

    Evidence Mutagenesis, EMSA, luciferase reporter assays, and cellular fractionation

    PMID:11313922 PMID:11464282

    Open questions at the time
    • Kinase phosphorylating Ser266 not identified
    • Single-lab biochemical studies
  13. 2002 High

    Genetically assigned MSK1/MSK2 as the kinases mediating stress- and mitogen-induced CREB/ATF1 phosphorylation and downstream immediate-early gene transcription.

    Evidence MSK1/MSK2 single and double knockout mice with phospho-immunoblot and Northern blot readouts

    PMID:11909979

    Open questions at the time
    • Residual phosphorylation indicates additional kinases
    • ATF1-specific (vs CREB) target effects not separated
  14. 2002 High

    Established the ERK → MSK1 → ATF1 Ser63 axis as required for EGF-induced c-jun activation, defining a specific mitogenic output of ATF1.

    Evidence Ser63→Ala mutagenesis, kinase-dead MSK1, U0126/dominant-negative MEK1, and reporter assays

    PMID:12414794

    Open questions at the time
    • Endogenous c-jun occupancy by ATF1 not directly mapped
    • Single-lab reporter system
  15. 2005 Medium

    Identified NOX1 as an ATF1 target in vascular smooth muscle, coupling mitochondrial/redox signaling to ATF1-dependent NADPH oxidase induction.

    Evidence Luciferase reporter, ATF1 siRNA, overexpression rescue, and pharmacological inhibitors

    PMID:15491278

    Open questions at the time
    • Direct ATF1 binding to NOX1 promoter by ChIP not shown
    • Single cell type
  16. 2006 Medium

    Placed CREB/ATF1 as an essential factor for adipogenic conversion acting downstream of or parallel to master adipogenic regulators.

    Evidence siRNA depletion with ectopic expression of C/EBP and PPARγ and adipogenesis assays in 3T3-L1 cells

    PMID:17071615

    Open questions at the time
    • Direct adipogenic target genes of ATF1 not defined
    • ATF1 vs CREB contribution not separated
  17. 2007 Medium

    Identified PIAS3 as an ATF1 interactor antagonizing ATF1's repressor function at the ferritin H ARE and showed ATF1 is SUMOylated, revealing repressive and post-translational regulatory facets.

    Evidence Yeast two-hybrid, co-IP, EMSA, siRNA, reporter, and sumoylation assays

    PMID:17565989

    Open questions at the time
    • Functional role of ATF1 SUMOylation unresolved
    • PIAS3-ATF1 interaction not validated in vivo
  18. 2008 High

    Defined ATF1 as a direct, p38-phosphorylated activator of hypoxia-induced UCP3, mapping a precise promoter element and linking ATF1 to metabolic adaptation.

    Evidence TF array screen, reporter mutagenesis, ChIP, shRNA, phospho-immunoblot, p38 inhibition

    PMID:18579531

    Open questions at the time
    • Generality across tissues untested
    • Cofactors at UCP3 promoter not identified
  19. 2010 High

    Identified RSK2 as a Ser63 ATF1 kinase whose activity drives Ras-mediated transformation, providing a pharmacologically targetable ATF1 signaling node.

    Evidence In vitro kinase assay, structural docking of eriodictyol, pulldown, RNAi, and focus formation assay

    PMID:21098035

    Open questions at the time
    • In vivo tumor relevance of RSK2-ATF1 axis untested here
    • ATF1 target genes mediating transformation undefined
  20. 2012 Medium

    Placed ATF1 as a direct miR-34c target controlling the Bcl-2/Bax ratio and germ cell apoptosis, revealing post-transcriptional regulation of ATF1 levels.

    Evidence 3'UTR luciferase reporter, siRNA, miR-34c inhibitor, western blot, apoptosis flow cytometry

    PMID:22479460

    Open questions at the time
    • Direct apoptotic target genes of ATF1 not mapped
    • Single cell model
  21. 2013 High

    Demonstrated in vivo that EWS/ATF1 in neural crest cells induces CCS-like sarcomas and directly drives FOS expression required for proliferation, establishing an oncogenic transcriptional output.

    Evidence Inducible transgenic mouse model, lineage tracing, and FOS siRNA knockdown

    PMID:23281395

    Open questions at the time
    • Full set of direct fusion targets not enumerated
    • Mechanism of ERK-independent Fos induction unclear
  22. 2014 High

    Revealed ATF1's role in the heat-shock response, where it partners with HSF1 and, in a phosphorylation-dependent manner, recruits BRG1 and p300/CBP to control HSP70 chromatin state and heat resistance.

    Evidence Co-IP, ChIP-seq, reporter assays, domain/phospho mutants, RNAi, and heat-shock survival assays

    PMID:25312646

    Open questions at the time
    • Whether HSF1 acetylation by ATF1-p300 is direct unproven
    • Generality beyond HSP70 untested
  23. 2019 Medium

    Showed risk-variant-driven upregulation of ATF1 promotes colorectal cancer growth and that ATF1 directly activates a set of oncogenic targets, extending its tumor-promoting role beyond the fusion context.

    Evidence RNAi screen, xenograft assays, ChIP-seq, RNA-seq, chromatin conformation, and reporter assays

    PMID:31204011

    Open questions at the time
    • Composite study with complex causal chains
    • Direct vs indirect target distinction incomplete
  24. 2022 High

    Resolved how the EWSR1 domain reprograms ATF1, retargeting it to novel distal enhancers and rewiring 3D chromatin to establish oncogenic and differentiation gene networks in CCS, with depletion reconfiguring connectivity and reactivating neural crest programs.

    Evidence ChIP-seq, ATAC-seq, Hi-C, EWSR1-ATF1 depletion, and RNA-seq in CCS cells; complemented by iPSC/enhancer silencing and lineage tracing (PMID 31488818)

    PMID:31488818 PMID:35477713

    Open questions at the time
    • Determinants of enhancer selection by the EWSR1 domain not fully defined
    • Translational targetability of the rewired network untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse upstream kinase inputs are integrated to produce context-specific ATF1 target gene selection, and how wild-type ATF1 versus the EWS/ATF1 fusion differentially engage chromatin and coactivators, remain incompletely defined.
  • No unified model of signal-to-target specificity
  • Genome-wide wild-type ATF1 occupancy map limited
  • Structural basis of EWS-domain-directed enhancer retargeting unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 5
Localization
GO:0005634 nucleus 3 GO:0000228 nuclear chromosome 1
Pathway
R-HSA-1643685 Disease 5 R-HSA-162582 Signal Transduction 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-1266738 Developmental Biology 2
Partners
BRCA1BRG1CREB1EWSR1HSF1MSK1P300/CBPPIAS3
Complex memberships
CREB/ATF1 dimerHSF1 transcription complex (HSP70 promoter)

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 ATF-1 contains a consensus PKA phosphorylation site and is capable of dimerizing with CREB; both ATF-1 homodimers and ATF-1/CREB heterodimers bind to the CRE but not the phorbol ester response element. ATF-1 mediates transcriptional activation in response to cAMP-dependent protein kinase A, and is more responsive than CREB to cAMP due to its smaller effect on basal expression. cDNA sequencing, in vitro dimerization assay, EMSA/DNA binding, transient transfection reporter assay with PKA The Journal of biological chemistry High 1655749
1993 The t(12;22)(q13;q12) chromosomal translocation fuses the N-terminal domain of EWS to the bZIP domain of ATF-1, producing a chimeric EWS/ATF1 protein associated with malignant melanoma of soft parts (clear cell sarcoma). RT-PCR, cDNA cloning, sequencing of hybrid transcripts from tumor specimens Nature genetics High 8401579
1993 ATF1 contains key serine residues required for a phosphorylation-induced conformational change; phosphorylation is modulated by ATF1 homodimerization and by ATF1 binding to DNA. One critical serine is not conserved in CREB/CREM, suggesting a specialized function of ATF1. In vitro phosphorylation assay, mutagenesis of serine residues, DNA binding stability assay Nucleic acids research Medium 8414969
1995 ATF-1 and CREB-1 bind constitutively to the HIF-1 DNA recognition site as homodimers or heterodimers, revealing a new binding specificity for ATF-1/CREB-1. PKA signaling (but not PKC) is involved in oxygen-sensing activity at this element. EMSA with competitor oligonucleotides and monoclonal antibody supershift, recombinant protein binding assay, reporter gene assay Nucleic acids research Medium 8524640
1995 EWS/ATF1 fusion protein acts as a strong constitutive transcriptional activator of some ATF1-binding promoters and represses others; the pattern of promoter activation in transfected cells correlates with promoter activity in MMSP-derived cell lines, indicating endogenous EWS/ATF1 de-regulates transcription. Transient transfection, reporter gene assay in JEG3 cells and MMSP cell lines Oncogene Medium 7753552
1996 FGF and cellular stress activate CREB and ATF-1 via p38 MAP kinase → MAPKAP kinase-2 signaling. MAPKAP kinase-2 phosphorylates CREB at Ser133 in vitro, and FGF/stress-induced phosphorylation of both CREB and ATF-1 is blocked by the p38 inhibitor SB 203580 at similar concentrations. Transfection of RK/p38 (but not p44 MAP kinase) activates Gal4-CREB-dependent transcription via Ser133. In vitro kinase assay, dominant negative Ras transfection, specific kinase inhibitor (SB203580), Gal4 reporter assay, cell fractionation kinase activity assays The EMBO journal High 8887554
1997 ATF-1 binds the ZII element of the EBV BZLF1 promoter (core motif TGACATCA) and transactivates it; deletion of ATF-1's DNA binding domain abolishes this transactivation. UV cross-linking identified ATF-1 as a 46/51 kDa protein within ZII-binding complexes. EMSA, UV cross-linking, antibody immunoprecipitation, cotransfection reporter assay with deletion mutants Virology Medium 9018131
1997 Phosphorylation of ATF-1 at Ser63 enhances its DNA binding activity in both homodimeric and heterodimeric (ATF-1/CREB) forms, and stimulates in vitro transcription from the Na,K-ATPase α1 subunit gene promoter, which has an asymmetrical ATF/CRE site. In vitro dephosphorylation, EMSA, in vitro transcription assay Nucleic acids research Medium 9016641
1997 ATF1 and CREB bind to two ATF/CRE motifs in the histone H4 promoter; ATF1 exists as two isoforms that partition differentially between nuclear matrix and non-matrix compartments, and both Site I and Site IV (nuclear matrix-associated) ATF/CRE motifs are required for ATF1- and CREB-induced transactivation of the H4 promoter. Protein-DNA interaction assays (EMSA), subnuclear fractionation, site-directed mutagenesis, transactivation reporter assay Biochemistry Medium 9398163
1998 EWS/ATF1 transcriptional activation does not require dimerization with other ATF family members; the EWS activation domain (EAD) can act directly and determinants of transactivation are dispersed throughout the EAD and cooperate synergistically. Mutational analysis in mammalian cells, reporter assay, yeast transactivation assay Oncogene Medium 9569031
1998 Dominant-negative ATF1 (point mutation in DNA binding domain) expressed stably in PC12D cells suppresses CRE reporter activity, reduces immediate early gene mRNA induction by forskolin, and blocks cAMP-induced neurite outgrowth, without affecting NGF-induced differentiation. This implicates the CREB/ATF1 heterodimer specifically in cAMP-dependent neuronal differentiation. Stable transfection of dominant-negative ATF1RL, CRE reporter assay, Northern blot for immediate early genes, morphological assessment of neurite outgrowth Journal of neurochemistry Medium 9489722
1999 Transcription of the TGF-β2 gene is dependent on CRE/ATF sites bound by CREB and ATF-1; the coactivators p300 and CBP up-regulate TGF-β2 promoter activity when CREB and ATF-1 are expressed together with kinases that phosphorylate CREB at Ser133 and ATF-1 at Ser63. Serine 133-phosphorylated CREB accumulates in nuclei of differentiated but not undifferentiated F9 cells. Transient transfection, co-expression with kinases, reporter assay, western blot for phospho-CREB The Journal of biological chemistry Medium 10567368
2000 BRCA1 physically interacts with ATF1 via the BRCA1 RING finger domain, as demonstrated in vitro, in yeast two-hybrid, and by co-immunoprecipitation in human cells. BRCA1 stimulates transcription from a CRE reporter and from the TNF-α promoter in a CRE-dependent manner. Yeast two-hybrid, in vitro pull-down, co-immunoprecipitation in human cells, transient transfection reporter assay The Journal of biological chemistry High 10945975
2001 Phosphorylation of serine 266 in the EWS IQ domain regulates the transcriptional activity of EWS/ATF1 (and EWS/FLI1). Elimination of phosphorylation significantly reduced DNA binding and reporter activation; phosphomimetic mutation partially restored wild-type activity. Phosphorylation also mediates cellular compartmentalization of EWS/ATF1. Mutagenesis, EMSA, luciferase reporter assay, cellular fractionation Oncogene Medium 11313922
2001 Degenerate Hexapeptide Repeats (DHRs) in the EWS activation domain contain conserved tyrosines that are required for transcriptional activation by EWS/ATF1; small regions (~30 residues) of the EAD trans-cooperate to produce potent tyrosine-dependent transactivation. Mutational analysis of EAD repeat elements, reporter assay in mammalian cells Oncogene Medium 11464282
2002 MSK1 and MSK2 are required for stress-induced phosphorylation of both CREB and ATF1 in primary fibroblasts. Mitogen-induced phosphorylation of CREB and ATF1 is greatly reduced but not abolished in MSK1/MSK2 double-knockout cells. Loss of both MSK1 and MSK2 reduces c-fos and junB transcription by ~50% in response to anisomycin or UV-C. Mouse MSK1/MSK2 single and double knockouts, immunoblot for phospho-CREB/ATF1, Northern blot for immediate early genes Molecular and cellular biology High 11909979
2002 ATF1 phosphorylation at Ser63 by MSK1 (activated downstream of ERK1/2) is required for EGF-induced c-jun promoter activation. A Ser63→Ala ATF1 mutant blocks EGF induction of transfected c-jun; kinase-dead MSK1 also blocks EGF induction. The ERK pathway (blocked by MEK1 inhibitor U0126 or dominant-negative MEK1) is required for MSK1 activation and ATF1 phosphorylation. Site-directed mutagenesis of ATF1 Ser63, dominant-negative kinase constructs, pharmacological inhibitors, reporter assay The Journal of biological chemistry High 12414794
1999 Intracellular delivery of an anti-ATF1 single-chain antibody (scFv4) into the CCS cell line SU-CCS-1 reduces CRE-driven reporter activity by 90% and causes loss of viability and apoptosis, demonstrating that EWS/ATF1 DNA-binding activity is required for maintenance of CCS tumor cell viability. Intracellular scFv antibody delivery, CRE reporter assay, TUNEL/flow cytometry apoptosis assay The Journal of biological chemistry Medium 10574952
2005 ATF-1 is an essential transcriptional activator of NOX1 (NADPH oxidase 1) in vascular smooth muscle cells. PGF2α- or PDGF-induced NOX1 mRNA induction is suppressed by mitochondrial respiratory chain inhibitors acting upstream of ATF-1 phosphorylation; ATF-1 siRNA knockdown reduces NOX1 induction, and ATF-1 overexpression rescues NOX1 induction suppressed by oligomycin. Luciferase reporter assay, RNA interference (siRNA), overexpression rescue, pharmacological inhibitors The Biochemical journal Medium 15491278
2006 Loss of CREB/ATF1 (by siRNA) blocks adipogenic conversion of 3T3-L1 cells even in the presence of ectopically expressed C/EBPα, C/EBPβ, or PPARγ2 individually, and prevents expression of PPARγ, C/EBPα, and adiponectin, indicating CREB/ATF1 acts downstream of or in parallel with master adipogenic regulators. siRNA depletion, ectopic expression of adipogenic regulators, adipogenesis assays (lipid accumulation, adipokine expression) The Journal of biological chemistry Medium 17071615
2007 PIAS3 interacts with ATF1 (identified by yeast two-hybrid screening) and antagonizes ATF1's function as a transcriptional repressor of the ferritin H ARE by decreasing ATF1 binding to the ARE. ATF1 is sumoylated, but PIAS3 does not appear to play a major role in SUMO1-mediated ATF1 sumoylation. ATF1 knockdown increases ferritin H expression. Yeast two-hybrid, co-immunoprecipitation, EMSA, siRNA knockdown, reporter assay, sumoylation assay The Journal of biological chemistry Medium 17565989
2008 ATF-1, identified via a transcription factor array screen, binds a 10-bp region of the UCP3 promoter (identified by site-directed mutagenesis and ChIP) and is required for hypoxia-induced UCP3 upregulation. ATF-1 is phosphorylated during hypoxia via p38 MAP kinase; shRNA knockdown of ATF-1 prevents hypoxia-mediated UCP3 upregulation. Transcription factor cDNA array screen, luciferase reporter + site-directed mutagenesis, ChIP, shRNA knockdown, western blot for phospho-ATF-1, p38 pharmacological inhibition The Journal of biological chemistry High 18579531
2010 RSK2 phosphorylates ATF1 at Ser-63 and enhances ATF1 transcriptional activity. In vitro pulldown assays combined with crystal structure docking show eriodictyol binds the RSK2 N-terminal kinase domain, inhibiting RSK2 activity and ATF1 phosphorylation. Knockdown of RSK2 or ATF1 suppresses Ras-mediated focus formation, indicating RSK2-ATF1 signaling drives neoplastic transformation. In vitro kinase assay, crystal structure docking, in vitro pulldown, RNAi knockdown, focus formation assay, reporter assay The Journal of biological chemistry High 21098035
2012 miR-34c directly binds the 3'UTR of ATF1 and reduces ATF1 protein (but not mRNA) levels; ATF1 knockdown decreases the Bcl-2/Bax ratio and induces apoptosis in GC-2 cells; miR-34c inhibition cannot rescue apoptosis in ATF1-knockdown cells, placing ATF1 downstream of miR-34c in the regulation of germ cell apoptosis. Luciferase 3'UTR reporter assay, siRNA knockdown, miR-34c inhibitor, western blot, flow cytometry for apoptosis PloS one Medium 22479460
2013 EWS/ATF1 expression in neural crest-derived cells in mice induces CCS-like sarcomas; EWS/ATF1 directly induces Fos expression in an ERK-independent manner, and FOS is required for EWS/ATF1-associated tumor cell proliferation (FOS siRNA attenuates growth). Inducible transgenic mouse model, lineage tracing, siRNA knockdown, gene expression analysis The Journal of clinical investigation High 23281395
2014 ATF1 interacts with HSF1 and is recruited to the HSP70 promoter in response to heat shock. The HSF1 transcription complex requires ATF1 phosphorylation for incorporation of BRG1 and p300/CBP. ATF1-BRG1 promotes active chromatin and HSP70 expression during heat shock; ATF1-p300/CBP accelerates shutdown of HSF1 DNA-binding during recovery, possibly via HSF1 acetylation. ATF1 markedly affects heat shock resistance. Co-immunoprecipitation, ChIP-seq, reporter assay, domain deletion/phosphorylation mutants, RNAi knockdown, heat shock survival assay Molecular and cellular biology High 25312646
2022 EWSR1-ATF1 displays a distinct DNA binding pattern that requires the EWSR1 domain and promotes ATF1 retargeting to new distal enhancer sites, leading to chromatin activation and establishment of a 3D regulatory network controlling oncogenic and differentiation gene signatures. EWSR1-ATF1 depletion reconfigures 3D connectivity and activates neural crest developmental programs. ChIP-seq, ATAC-seq, Hi-C/3D chromatin conformation, EWSR1-ATF1 depletion, RNA-seq in CCS cells Nature communications High 35477713
2019 ATF1 facilitates cell proliferation and promotes CRC xenograft growth by affecting cell apoptosis. Two risk variants in the ATF1 promoter and first intron facilitate a promoter-enhancer interaction mediated by SP1 and GATA3, upregulating ATF1 expression. ChIP-seq shows ATF1 activates a subset of target genes including BRAF, NRAS, MYC, BIRC2, and MAML2 related to apoptosis, Wnt, TGF-β, and MAPK pathways. RNAi screen, xenograft growth assay, ChIP-seq, RNA-seq, chromatin conformation assay, luciferase reporter American journal of human genetics Medium 31204011
2019 EWS/ATF1 binds cell type-specific enhancer regions in CCS cells; epigenetic silencing at these enhancers induces senescence and inhibits CCS cell growth through altered EWS/ATF1 binding. EWS/ATF1 expression induces oncogene-induced senescence in most cell types but prevents it in sarcoma-permissive cells, and Tppp3-expressing cells in peripheral nerves are identified as a cell-of-origin. iPSC reprogramming, inducible EWS/ATF1 expression, ChIP-seq, epigenetic silencing, lineage tracing Nature communications High 31488818

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 FGF and stress regulate CREB and ATF-1 via a pathway involving p38 MAP kinase and MAPKAP kinase-2. The EMBO journal 569 8887554
1993 EWS and ATF-1 gene fusion induced by t(12;22) translocation in malignant melanoma of soft parts. Nature genetics 455 8401579
1996 Conjugation, meiosis, and the osmotic stress response are regulated by Spc1 kinase through Atf1 transcription factor in fission yeast. Genes & development 376 8824587
2002 MSK1 and MSK2 are required for the mitogen- and stress-induced phosphorylation of CREB and ATF1 in fibroblasts. Molecular and cellular biology 375 11909979
1996 The Atf1 transcription factor is a target for the Sty1 stress-activated MAP kinase pathway in fission yeast. Genes & development 324 8824588
2011 EWSR1-ATF1 fusion is a novel and consistent finding in hyalinizing clear-cell carcinoma of salivary gland. Genes, chromosomes & cancer 292 21484932
1995 Schizosaccharomyces pombe atf1+ encodes a transcription factor required for sexual development and entry into stationary phase. The EMBO journal 230 8557039
1991 The cAMP-regulated enhancer-binding protein ATF-1 activates transcription in response to cAMP-dependent protein kinase A. The Journal of biological chemistry 198 1655749
2012 Tumors with EWSR1-CREB1 and EWSR1-ATF1 fusions: the current status. The American journal of surgical pathology 195 22510762
1995 The transcription factors ATF-1 and CREB-1 bind constitutively to the hypoxia-inducible factor-1 (HIF-1) DNA recognition site. Nucleic acids research 186 8524640
2009 Detection and characterization of EWSR1/ATF1 and EWSR1/CREB1 chimeric transcripts in clear cell sarcoma (melanoma of soft parts). Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 178 19561568
1997 Discrete roles of the Spc1 kinase and the Atf1 transcription factor in the UV response of Schizosaccharomyces pombe. Molecular and cellular biology 170 9154834
2007 EWSR1-CREB1 and EWSR1-ATF1 fusion genes in angiomatoid fibrous histiocytoma. Clinical cancer research : an official journal of the American Association for Cancer Research 168 18094413
2002 Molecular diagnosis of clear cell sarcoma: detection of EWS-ATF1 and MITF-M transcripts and histopathological and ultrastructural analysis of 12 cases. The Journal of molecular diagnostics : JMD 144 11826187
1998 Phosphorylation and association with the transcription factor Atf1 regulate localization of Spc1/Sty1 stress-activated kinase in fission yeast. Genes & development 139 9585506
1997 Transcription factor Mts1/Mts2 (Atf1/Pcr1, Gad7/Pcr1) activates the M26 meiotic recombination hotspot in Schizosaccharomyces pombe. Proceedings of the National Academy of Sciences of the United States of America 137 9391101
2002 Molecular genetic characterization of the EWS/ATF1 fusion gene in clear cell sarcoma of tendons and aponeuroses. International journal of cancer 116 11992546
2000 Genetic characterization of angiomatoid fibrous histiocytoma identifies fusion of the FUS and ATF-1 genes induced by a chromosomal translocation involving bands 12q13 and 16p11. Cancer genetics and cytogenetics 116 11063792
2014 The fungal aroma gene ATF1 promotes dispersal of yeast cells through insect vectors. Cell reports 113 25310977
2012 MicroRNA-34c enhances murine male germ cell apoptosis through targeting ATF1. PloS one 105 22479460
2005 Fusion of the EWSR1 and ATF1 genes without expression of the MITF-M transcript in angiomatoid fibrous histiocytoma. Genes, chromosomes & cancer 105 15884099
2006 Depletion of cAMP-response element-binding protein/ATF1 inhibits adipogenic conversion of 3T3-L1 cells ectopically expressing CCAAT/enhancer-binding protein (C/EBP) alpha, C/EBP beta, or PPAR gamma 2. The Journal of biological chemistry 90 17071615
2017 A Subset of Malignant Mesotheliomas in Young Adults Are Associated With Recurrent EWSR1/FUS-ATF1 Fusions. The American journal of surgical pathology 89 28505004
2011 EWSR1-ATF1 chimeric transcript in a myoepithelial tumor of soft tissue: a case report. Human pathology 86 22154050
2008 Transcription factors Pcr1 and Atf1 have distinct roles in stress- and Sty1-dependent gene regulation. Eukaryotic cell 81 18375616
2006 Regulation of Schizosaccharomyces pombe Atf1 protein levels by Sty1-mediated phosphorylation and heterodimerization with Pcr1. The Journal of biological chemistry 80 17182615
1995 Promoters containing ATF-binding sites are de-regulated in cells that express the EWS/ATF1 oncogene. Oncogene 79 7753552
2011 Interrogation of related clinical pan-azole-resistant Aspergillus fumigatus strains: G138C, Y431C, and G434C single nucleotide polymorphisms in cyp51A, upregulation of cyp51A, and integration and activation of transposon Atf1 in the cyp51A promoter. Antimicrobial agents and chemotherapy 78 21876055
2008 Primary intracerebral angiomatoid fibrous histiocytoma: report of a case with a t(12;22)(q13;q12) causing type 1 fusion of the EWS and ATF-1 genes. The American journal of surgical pathology 78 18300800
2002 ATF1 phosphorylation by the ERK MAPK pathway is required for epidermal growth factor-induced c-jun expression. The Journal of biological chemistry 71 12414794
2005 EWS-ATF1 fusion transcripts in gastrointestinal tumors previously diagnosed as malignant melanoma. Human pathology 66 15712185
2005 Vasoactive intestinal peptide upregulates MUC2 intestinal mucin via CREB/ATF1. American journal of physiology. Gastrointestinal and liver physiology 66 16227528
2006 Leptin signaling in neurotensin neurons involves STAT, MAP kinases ERK1/2, and p38 through c-Fos and ATF1. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 65 17077290
2002 Fusion of the FUS and ATF1 genes in a large, deep-seated angiomatoid fibrous histiocytoma. Diagnostic molecular pathology : the American journal of surgical pathology, part B 62 12218455
2013 The ATF/CREB transcription factor Atf1 is essential for full virulence, deoxynivalenol production, and stress tolerance in the cereal pathogen Fusarium graminearum. Molecular plant-microbe interactions : MPMI 59 23945004
2017 LncRNA GHET1 activated by H3K27 acetylation promotes cell tumorigenesis through regulating ATF1 in hepatocellular carcinoma. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 57 28772210
2004 A cooperative role for Atf1 and Pap1 in the detoxification of the oxidative stress induced by glucose deprivation in Schizosaccharomyces pombe. The Journal of biological chemistry 56 15247218
2000 BRCA1 physically and functionally interacts with ATF1. The Journal of biological chemistry 56 10945975
2010 Genomic binding profiling of the fission yeast stress-activated MAPK Sty1 and the bZIP transcriptional activator Atf1 in response to H2O2. PloS one 55 20661279
1999 Transcriptional regulation of the transforming growth factor-beta2 promoter by cAMP-responsive element-binding protein (CREB) and activating transcription factor-1 (ATF-1) is modulated by protein kinases and the coactivators p300 and CREB-binding protein. The Journal of biological chemistry 55 10567368
2010 Eriodictyol inhibits RSK2-ATF1 signaling and suppresses EGF-induced neoplastic cell transformation. The Journal of biological chemistry 54 21098035
2019 Systematic Functional Interrogation of Genes in GWAS Loci Identified ATF1 as a Key Driver in Colorectal Cancer Modulated by a Promoter-Enhancer Interaction. American journal of human genetics 53 31204011
2005 Essential role of ATF-1 in induction of NOX1, a catalytic subunit of NADPH oxidase: involvement of mitochondrial respiratory chain. The Biochemical journal 53 15491278
2007 Atf1 is a target of the mitogen-activated protein kinase Pmk1 and regulates cell integrity in fission yeast. Molecular biology of the cell 52 17881729
2014 Heme oxygenase-1 regulates dendritic cell function through modulation of p38 MAPK-CREB/ATF1 signaling. The Journal of biological chemistry 51 24719331
2014 ATF1 modulates the heat shock response by regulating the stress-inducible heat shock factor 1 transcription complex. Molecular and cellular biology 48 25312646
2012 RNAi keeps Atf1-bound stress response genes in check at nuclear pores. Genes & development 48 22431512
2003 The Saccharomyces cerevisiae alcohol acetyl transferase gene ATF1 is a target of the cAMP/PKA and FGM nutrient-signalling pathways. FEMS yeast research 48 14654433
1998 Transcriptional co-regulation of Saccharomyces cerevisiae alcohol acetyltransferase gene, ATF1 and delta-9 fatty acid desaturase gene, OLE1 by unsaturated fatty acids. Yeast (Chichester, England) 45 9675816
1997 Malignant melanoma of the soft parts (clear-cell sarcoma): confirmation of EWS and ATF-1 gene fusion caused by a t(12;22) translocation. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 45 9160316
1996 The CREB, ATF-1, and ATF-2 transcription factors from bovine leukemia virus-infected B lymphocytes activate viral expression. Journal of virology 45 8627725
2012 Endobronchial pulmonary angiomatoid fibrous histiocytoma: two cases with EWSR1-CREB1 and EWSR1-ATF1 fusions. The American journal of surgical pathology 44 22588066
2008 ATF-1 transcription factor regulates the expression of ccg-1 and cat-1 genes in response to fludioxonil under OS-2 MAP kinase in Neurospora crassa. Fungal genetics and biology : FG & B 44 18948219
1999 Molecular mechanism of the multiple regulation of the Saccharomyces cerevisiae ATF1 gene encoding alcohol acetyltransferase. Yeast (Chichester, England) 44 10487921
2013 EWS/ATF1 expression induces sarcomas from neural crest-derived cells in mice. The Journal of clinical investigation 43 23281395
2008 Distinct regions of ATF/CREB proteins Atf1 and Pcr1 control recombination hotspot ade6-M26 and the osmotic stress response. Nucleic acids research 43 18375981
2004 Atf1-Pcr1-M26 complex links stress-activated MAPK and cAMP-dependent protein kinase pathways via chromatin remodeling of cgs2+. The Journal of biological chemistry 43 15448137
2013 What the EWSR1-ATF1 fusion has taught us about hyalinizing clear cell carcinoma. Head and neck pathology 41 23459838
2000 Role of Atf1 and Pap1 in the induction of the catalase gene of fission yeast schizosaccharomyces pombe. Journal of biochemistry 41 10731689
1997 Characterization of proteins binding to the ZII element in the Epstein-Barr virus BZLF1 promoter: transactivation by ATF1. Virology 40 9018131
2008 Int6/eIF3e promotes general translation and Atf1 abundance to modulate Sty1 MAPK-dependent stress response in fission yeast. The Journal of biological chemistry 39 18502752
1995 Down-regulation of the cyclin A promoter in differentiating human embryonal carcinoma cells is mediated by depletion of ATF-1 and ATF-2 in the complex at the ATF/CRE site. Experimental cell research 39 7843287
2022 EWSR1-ATF1 dependent 3D connectivity regulates oncogenic and differentiation programs in Clear Cell Sarcoma. Nature communications 37 35477713
1998 The EWS/ATF1 fusion protein contains a dispersed activation domain that functions directly. Oncogene 37 9569031
1993 In vitro phosphorylation studies of a conserved region of the transcription factor ATF1. Nucleic acids research 35 8414969
2007 PIAS3 interacts with ATF1 and regulates the human ferritin H gene through an antioxidant-responsive element. The Journal of biological chemistry 34 17565989
1998 Dominant negative ATF1 blocks cyclic AMP-induced neurite outgrowth in PC12D cells. Journal of neurochemistry 34 9489722
1995 Transcription factors RFX1/EF-C and ATF-1 associate with the adenovirus E1A-responsive element of the human proliferating cell nuclear antigen promoter. Nucleic acids research 34 7479004
2023 Inflammatory and Nested Testicular Sex Cord Tumor: A Novel Neoplasm With Aggressive Clinical Behavior and Frequent EWSR1::ATF1 Gene Fusions. The American journal of surgical pathology 33 36791251
2020 Intracranial Myxoid Mesenchymal Tumor With EWSR1-ATF1 Fusion. Journal of neuropathology and experimental neurology 33 32016322
2021 Blockade of AMPK-Mediated cAMP-PKA-CREB/ATF1 Signaling Synergizes with Aspirin to Inhibit Hepatocellular Carcinoma. Cancers 32 33917483
2021 NEDD4 triggers FOXA1 ubiquitination and promotes colon cancer progression under microRNA-340-5p suppression and ATF1 upregulation. RNA biology 31 33530829
2017 Deciphering the role of the signal- and Sty1 kinase-dependent phosphorylation of the stress-responsive transcription factor Atf1 on gene activation. The Journal of biological chemistry 31 28652406
2006 Docosahexaenoic acid consumption inhibits deoxynivalenol-induced CREB/ATF1 activation and IL-6 gene transcription in mouse macrophages. The Journal of nutrition 31 16424113
2019 Cell-type dependent enhancer binding of the EWS/ATF1 fusion gene in clear cell sarcomas. Nature communications 30 31488818
2018 Clear Cell Odontogenic Carcinoma: Occurrence of EWSR1-CREB1 as Alternative Fusion Gene to EWSR1-ATF1. Head and neck pathology 30 30047065
2009 The cell surface protein gene ecm33+ is a target of the two transcription factors Atf1 and Mbx1 and negatively regulates Pmk1 MAPK cell integrity signaling in fission yeast. Molecular biology of the cell 30 20032302
2001 Phosphorylation of the EWS IQ domain regulates transcriptional activity of the EWS/ATF1 and EWS/FLI1 fusion proteins. Oncogene 29 11313922
2017 miR-30a radiosensitizes non-small cell lung cancer by targeting ATF1 that is involved in the phosphorylation of ATM. Oncology reports 28 28259977
2014 EWSR1 and ATF1 rearrangements in clear cell odontogenic carcinoma: presentation of a case. Oral surgery, oral medicine, oral pathology and oral radiology 28 24721473
2006 Visceral clear cell sarcoma of soft tissue with confirmation by EWS-ATF1 fusion detection. Ultrastructural pathology 28 16517477
2017 ALD5, PAD1, ATF1 and ATF2 facilitate the catabolism of coniferyl aldehyde, ferulic acid and p-coumaric acid in Saccharomyces cerevisiae. Scientific reports 27 28205618
2008 ATF-1 is a hypoxia-responsive transcriptional activator of skeletal muscle mitochondrial-uncoupling protein 3. The Journal of biological chemistry 27 18579531
2014 Hyalinizing clear cell carcinoma with EWSR1-ATF1 fusion gene: report of three cases with molecular analyses. Virchows Archiv : an international journal of pathology 26 25359601
1999 Tumor cell viability in clear cell sarcoma requires DNA binding activity of the EWS/ATF1 fusion protein. The Journal of biological chemistry 26 10574952
2020 LINC00665/miR-9-5p/ATF1 is a novel axis involved in the progression of colorectal cancer. Human cell 25 32776307
2017 ATF1 and RAS in exosomes are potential clinical diagnostic markers for cervical cancer. Cell biochemistry and function 25 29023897
2019 Long non-coding RNA RP11-552M11.4 favors tumorigenesis and development of cervical cancer via modulating miR-3941/ATF1 signaling. International journal of biological macromolecules 24 30790638
2019 Transcription Factor Atf1 Regulates Expression of Cellulase and Xylanase Genes during Solid-State Fermentation of Ascomycetes. Applied and environmental microbiology 24 31604764
2009 The transcription factor Atf1 binds and activates the APC/C ubiquitin ligase in fission yeast. The Journal of biological chemistry 24 19584054
2009 The presence and activation of two essential transcription factors (cAMP response element-binding protein and cAMP-dependent transcription factor ATF1) in the two-cell mouse embryo. Biology of reproduction 24 19776387
2008 Flavour formation in fungi: characterisation of KlAtf, the Kluyveromyces lactis orthologue of the Saccharomyces cerevisiae alcohol acetyltransferases Atf1 and Atf2. Applied microbiology and biotechnology 24 18309479
1997 Phosphorylation of ATF-1 enhances its DNA binding and transcription of the Na,K-ATPase alpha 1 subunit gene promoter. Nucleic acids research 24 9016641
1997 ATF1 and CREB trans-activate a cell cycle regulated histone H4 gene at a distal nuclear matrix associated promoter element. Biochemistry 23 9398163
2005 Association of the t(12;22)(q13;q12) EWS/ATF1 rearrangement with polyphenotypic round cell sarcoma of bone: a case report. The American journal of surgical pathology 22 16327442
2001 A repetitive element containing a critical tyrosine residue is required for transcriptional activation by the EWS/ATF1 oncogene. Oncogene 22 11464282
2015 The human ATF1 rs11169571 polymorphism increases essential hypertension risk through modifying miRNA binding. FEBS letters 21 26149214
2009 Stress-induced phosphorylation of S. pombe Atf1 abrogates its interaction with F box protein Fbh1. Current biology : CB 21 19836238
1998 5-HT3 receptor activation is required for induction of striatal c-Fos and phosphorylation of ATF-1 by amphetamine. Synapse (New York, N.Y.) 21 9704883
2017 Establishment and characterization of a clear cell odontogenic carcinoma cell line with EWSR1-ATF1 fusion gene. Oral oncology 20 28559020

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