Affinage

CEBPG

CCAAT/enhancer-binding protein gamma · UniProt P53567

Length
150 aa
Mass
16.4 kDa
Annotated
2026-06-09
11 papers in source corpus 9 papers cited in narrative 9 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

CEBPG (Ig/EBP-1, GPE1-BP) is a basic-leucine zipper transcription factor that recognizes CCAAT/enhancer-type DNA elements and functions as a context-dependent transcriptional activator across stress-response and cancer programs (PMID:2121606, PMID:33163273). It was the first C/EBP family member shown to heterodimerize with C/EBP through its leucine-repeat region, and it binds E sites in immunoglobulin enhancer/promoter elements as well as C/EBP sites in viral and hepatic promoters (PMID:2121606); it also recognizes the LPS-inducible GPE1 element of the G-CSF promoter (PMID:1709121). Through direct promoter and enhancer occupancy, CEBPG drives diverse target genes: it upregulates the DNA-repair nuclease ERCC5/XPG in concert with adjacent E2F1 and YY1 binding (PMID:17893230), activates PI3K-AKT proliferative genes (CCND1, MYC, CDK2) in esophageal squamous carcinoma (PMID:33163273), and induces the translational regulator EIF4EBP1 to promote AML proliferation (PMID:34743716). In stress-adaptation programs CEBPG partners with ATF4: the ATF4-CEBPG heterodimer transactivates RETREG1 to activate reticulophagy and protect against lipotoxicity (PMID:40437698), and CEBPG also regulates the ER-stress genes ERN1 and TMBIM6 via enhancer-associated transcription in cancer-associated fibroblasts to support metastasis (PMID:42227941). It additionally suppresses ferroptosis by transactivating SLC7A11 (PMID:37210575). No structural model of CEBPG-DNA or CEBPG-heterodimer complexes is characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1990 High

    Established CEBPG as a bZIP DNA-binding protein and the first C/EBP family member capable of heterodimerization, defining its core biochemical mode of action.

    Evidence Fusion-protein DNA-binding assays and leucine-zipper heterodimerization assays on IgH enhancer, VH1 promoter, RSV LTR and albumin promoter elements

    PMID:2121606

    Open questions at the time
    • No genome-wide target map at this stage
    • Functional consequence of heterodimerization on transcription not yet shown
    • No structural resolution of the dimer interface
  2. 1991 Medium

    Identified a physiological DNA target by showing CEBPG binds the LPS-inducible GPE1 element of the G-CSF promoter, linking it to inducible inflammatory gene expression.

    Evidence cDNA cloning, COS cell transfection and nuclear-extract DNA-binding assay

    PMID:1709121

    Open questions at the time
    • Transcriptional activation of endogenous G-CSF not demonstrated
    • Single lab
    • Dimer partner at GPE1 not defined
  3. 2007 Medium

    Demonstrated CEBPG functions as a direct transcriptional regulator of a DNA-repair gene, showing it activates ERCC5/XPG within a combinatorial promoter context.

    Evidence Luciferase reporter assays and EMSA in two cell lines with E2F1 and YY1 co-occupancy

    PMID:17893230

    Open questions at the time
    • Cellular DNA-repair phenotype of CEBPG loss not tested
    • Interplay logic with E2F1/YY1 not mechanistically resolved
    • No in vivo validation
  4. 2020 Medium

    Placed CEBPG as a driver of proliferative signaling in cancer by mapping its direct enhancer/promoter binding to PI3K-AKT pathway genes.

    Evidence ChIP-seq plus in vitro proliferation/migration and in vivo mouse models with knockdown/overexpression in esophageal squamous cell carcinoma

    PMID:33163273

    Open questions at the time
    • Direct activation of each named target not individually validated by reporter
    • Dimer partner in this context unknown
    • Single lab
  5. 2021 Medium

    Defined a CEBPG transcriptional axis in AML by placing it upstream of EIF4EBP1 through epistatic knockdown.

    Evidence shRNA knockdown, RNA-seq, public ChIP-seq, proliferation and flow cytometry assays

    PMID:34743716

    Open questions at the time
    • Direct CEBPG occupancy at EIF4EBP1 used public data rather than primary ChIP
    • Translational-control mechanism downstream not dissected
    • Single lab
  6. 2023 Medium

    Linked CEBPG to ferroptosis resistance by showing direct transactivation of SLC7A11, extending its role into metabolic cell-death control.

    Evidence CUT&Tag chromatin profiling, dual luciferase reporter, RNA-seq, knockdown and orthotopic ovarian cancer model

    PMID:37210575

    Open questions at the time
    • Upstream signals controlling CEBPG in this context unknown
    • Dimer partner not identified
    • Single lab
  7. 2025 Medium

    Identified the ATF4-CEBPG heterodimer as a specific transactivator of RETREG1, connecting the factor to reticulophagy-mediated protection from lipotoxicity.

    Evidence Reciprocal Co-IP, ChIP at promoter/enhancer sites, knockdown, and in vitro/in vivo mouse models

    PMID:40437698

    Open questions at the time
    • Relative contribution of CEBPG homodimer vs ATF4 heterodimer not quantified
    • Stoichiometry of the heterodimer not resolved
    • Single lab
  8. 2025 Low

    Proposed that ATF4 and CEBPG jointly establish an adaptive metabolic program in nutrient-stressed CD8+ T cells, suggesting a role in immune-cell metabolic resilience.

    Evidence Gene-regulatory and metabolic network analysis in CD8+ T cells under nutrient stress (preprint)

    PMID:bio_10.1101_2025.01.22.632829

    Open questions at the time
    • Preprint without direct protein-level binding or mutagenesis data
    • Direct target genes not defined
    • Causality vs correlation in network inference unresolved
  9. 2026 Medium

    Extended CEBPG into the tumor microenvironment by showing enhancer-associated regulation of ER-stress genes ERN1 and TMBIM6 that drives cancer-associated fibroblast phenotypes and metastasis.

    Evidence H3K27ac ChIP chromatin landscape analysis, enhancer-associated transcription assays, knockdown and orthotopic oral squamous cell carcinoma models

    PMID:42227941

    Open questions at the time
    • Direct CEBPG binding at ERN1/TMBIM6 enhancers vs broader chromatin state not fully separated
    • Signal that activates CEBPG in CAFs unknown
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CEBPG dimer-partner choice (homodimer vs C/EBP vs ATF4) is regulated to select among its diverse target programs across cell types remains unresolved.
  • No structural model of CEBPG-DNA or heterodimer complexes
  • Determinants of context-specific target selection unknown
  • Upstream signaling controlling CEBPG activity across contexts undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0003677 DNA binding 3
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-8953897 Cellular responses to stimuli 2
Partners
ATF4E2F1YY1

Evidence

Reading pass · 9 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 Ig/EBP-1 (CEBPG) is a basic-leucine zipper protein that binds specifically to E sites in the IgH enhancer and VH1 promoter, as well as to C/EBP binding sites in the RSV LTR and murine albumin promoter. CEBPG heterodimerizes with C/EBP through its leucine repeat region, making it the first C/EBP family member shown to form heterodimers with C/EBP. Fusion protein DNA-binding assay, sequence analysis, heterodimerization assay (leucine zipper region) Genes & development High 2121606
1991 GPE1-BP (CEBPG) binds specifically to GPE1, a cis-acting element of the G-CSF gene promoter that functions as an LPS-inducible element; nuclear extract from COS cells transfected with the cDNA showed GPE1-binding activity. cDNA cloning, transfection of COS cells, nuclear extract DNA-binding assay FEBS letters Medium 1709121
2007 CEBPG transcriptionally upregulates ERCC5/XPG expression by binding to a recognition site in the ERCC5 5' regulatory region; this regulation is modified by E2F1 and YY1, which bind adjacent sites on sense and antisense strands respectively. CEBPG, E2F1, and YY1 binding to their respective sites was confirmed by EMSA. Expression vector transfection, luciferase reporter assay, electrophoretic mobility shift assay (EMSA) Carcinogenesis Medium 17893230
2020 CEBPG activates the PI3K-AKT signaling pathway in esophageal squamous cell carcinoma by directly binding to distal enhancers and/or promoters of pathway genes including CCND1, MYC, and CDK2, promoting cell proliferation and migration. ChIP-seq, in vitro proliferation/migration assays, in vivo mouse model, knockdown/overexpression American journal of cancer research Medium 33163273
2021 CEBPG promotes AML cell proliferation by transcriptionally activating EIF4EBP1 (a known repressor of translation); knockdown of EIF4EBP1 downstream of CEBPG reduced AML cell growth, placing CEBPG upstream of EIF4EBP1 in AML progression. shRNA knockdown, RNA-seq, ChIP-seq (public data), CCK-8 proliferation assay, western blotting, flow cytometry Cancer cell international Medium 34743716
2023 CEBPG suppresses ferroptosis in ovarian cancer cells by directly binding to the promoter of SLC7A11 (a key ferroptosis regulator) and transcriptionally activating its expression, as demonstrated by CUT&Tag and dual luciferase reporter assays. CUT&Tag chromatin profiling, dual luciferase reporter assay, RNA-seq, knockdown, in vivo orthotopic mouse model Journal of translational medicine Medium 37210575
2025 ATF4 forms a heterodimer with CEBPG, and this heterodimer transcriptionally upregulates RETREG1 (reticulophagy regulator 1) by binding to identified sites in its promoter and enhancer regions, activating reticulophagy to protect against lipotoxicity. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), knockdown experiments, in vitro and in vivo mouse models Autophagy Medium 40437698
2026 CEBPG regulates transcription of ERN1 and TMBIM6 in cancer-associated fibroblasts in an enhancer-associated manner; disruption of the CEBPG-IRE1α/TMBIM6 axis attenuated myoCAF properties and abrogated palmitic acid-driven metastasis of oral squamous cell carcinoma. Chromatin landscape analysis (H3K27ac ChIP), enhancer-associated transcription assays, knockdown, in vivo orthotopic tumor models Advanced science Medium 42227941
2025 In CD8+ T cells under nutrient stress, ATF4 and CEBPG jointly establish an adaptive metabolic program that promotes amino acid synthesis and uptake while maintaining mitochondrial anaplerosis, preventing failure of central carbon metabolism. Gene-regulatory and metabolic network analysis in CD8+ T cells under nutrient stress (transcriptional and metabolic profiling) bioRxivpreprint Low bio_10.1101_2025.01.22.632829

Source papers

Stage 0 corpus · 11 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1990 Ig/EBP-1: a ubiquitously expressed immunoglobulin enhancer binding protein that is similar to C/EBP and heterodimerizes with C/EBP. Genes & development 254 2121606
2023 CEBPG suppresses ferroptosis through transcriptional control of SLC7A11 in ovarian cancer. Journal of translational medicine 38 37210575
1991 Molecular cloning of cDNA and a chromosomal gene encoding GPE1-BP, a nuclear protein which binds to granulocyte colony-stimulating factor promoter element 1. FEBS letters 37 1709121
2007 CEBPG regulates ERCC5/XPG expression in human bronchial epithelial cells and this regulation is modified by E2F1/YY1 interactions. Carcinogenesis 33 17893230
2005 CEBPG transcription factor correlates with antioxidant and DNA repair genes in normal bronchial epithelial cells but not in individuals with bronchogenic carcinoma. BMC cancer 31 16255782
2020 CEBPG promotes esophageal squamous cell carcinoma progression by enhancing PI3K-AKT signaling. American journal of cancer research 29 33163273
2021 CEBPG promotes acute myeloid leukemia progression by enhancing EIF4EBP1. Cancer cell international 11 34743716
2013 CEBPG Exhibits Allele-Specific Expression in Human Bronchial Epithelial Cells. Gene regulation and systems biology 10 23888109
2025 RETREG1-mediated reticulophagy is activated by an ATF4-CEBPG/C/EBPγ heterodimer and confers protection against lipotoxicity. Autophagy 4 40437698
2021 Interacting C/EBPg and YBP regulate DNA methyltransferase 1 expression in Bombyx mori embryos and ovaries. Insect biochemistry and molecular biology 3 34010702
2026 CEBPG-Mediated Palmitic Acid Adaptation of Cancer-Associated Fibroblasts Drives Metastasis of Oral Squamous Cell Carcinoma. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 42227941

Missed literature

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

No submissions yet.