Affinage

CEBPD

CCAAT/enhancer-binding protein delta · UniProt P49716

Length
269 aa
Mass
28.5 kDa
Annotated
2026-04-28
100 papers in source corpus 31 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CEBPD is an inducible bZIP transcription factor that functions as a central integrator of inflammatory, growth-arrest, and stress-responsive gene programs by forming homodimers and heterodimers with C/EBPβ, PU.1, and Pit1 to activate or repress diverse target promoters including C3, COX-2, TLR8, PRL, SOD1, ABCB1/ABCC2, FN1, CDC27/APC3, and PRKDC (PMID:1741402, PMID:8385337, PMID:20439707, PMID:27435393, PMID:37059730). Its transcriptional activity is tightly modulated by p38 MAPK-mediated phosphorylation at a docking site between residues 75–85, SUMO1 modification at K120 that switches CEBPD from an activator to a repressor by recruiting HDAC1/3, and ubiquitin-dependent nuclear proteasomal degradation (PMID:15694370, PMID:18619497, PMID:12554732). Beyond transcription, CEBPD performs a scaffolding function by bridging FANCD2 and importin 4 to promote FANCD2 nuclear import and monoubiquitination required for DNA damage repair (PMID:20805509). CEBPD expression is controlled upstream by IL-1/IL-6/LPS, cAMP, EGFR/STAT3, hypoxia/HIF, and BRD4-dependent enhancer activity, and is terminated by Miz1-HDAC1-mediated transcriptional repression (PMID:8385337, PMID:7680115, PMID:23525087, PMID:33768129, PMID:37059730).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1992 High

    Establishing that CEBPD heterodimerizes with C/EBPβ and that the heterodimer binds the same DNA elements as homodimers resolved the fundamental question of how the C/EBP family achieves combinatorial transcriptional control.

    Evidence In vitro heterodimerization, EMSA, and luciferase reporter assays

    PMID:1741402

    Open questions at the time
    • Stoichiometry and relative affinity of heterodimer vs. homodimer at endogenous promoters unknown
    • In vivo relevance of heterodimerization not demonstrated
  2. 1993 High

    Demonstrating that CEBPD is the principal IL-1- and IL-6-inducible C/EBP family member that transactivates acute-phase gene promoters (C3, hemopexin, haptoglobin, CRP) established CEBPD as the effector linking cytokine signaling to the hepatic acute-phase response.

    Evidence Supershift EMSA, Western blot of nuclear accumulation, and reporter assays in Hep3B hepatoma cells after IL-1 or IL-6 treatment

    PMID:7680115 PMID:8385337

    Open questions at the time
    • Contribution of CEBPD relative to C/EBPβ at endogenous acute-phase loci not quantified
    • In vivo acute-phase response in CEBPD-null animals not yet tested at this stage
  3. 1995 High

    Identifying that CEBPD synergizes with PU.1 via direct leucine-zipper-to-Ets-domain contact, and that growth hormone transcriptionally induces CEBPD independently of insulin, broadened the upstream signals and cooperative partners controlling CEBPD activity.

    Evidence Far Western, deletion mutagenesis, EMSA, and synergy reporter assay for PU.1; Northern blot with cycloheximide superinduction for GH induction

    PMID:7594592 PMID:7760844

    Open questions at the time
    • Genomic targets co-regulated by CEBPD–PU.1 not identified
    • Signaling intermediates between GH receptor and CEBPD promoter not mapped
  4. 1996 High

    Showing that CEBPD behaves as a cAMP-inducible immediate-early gene in astrocytes and that its forced expression enhances glycogen resynthesis established a metabolic effector role outside the immune system.

    Evidence Northern blot with protein synthesis inhibitors and CEBPD overexpression glycogen resynthesis assay in cortical astrocytes

    PMID:8558260

    Open questions at the time
    • Direct target genes mediating glycogen resynthesis not identified
    • In vivo brain metabolic phenotype of CEBPD loss not tested
  5. 1997 High

    Demonstrating that CEBPD is induced during G0 arrest and that antisense-mediated loss delays growth arrest provided the first functional evidence that CEBPD is required for cell cycle exit.

    Evidence Antisense knockdown, BrdU incorporation, Northern/Western blot in mammary epithelial cells

    PMID:9045647

    Open questions at the time
    • Direct transcriptional targets mediating G0 arrest unknown at this point
    • Mechanism distinguishing CEBPD from C/EBPα in growth arrest not resolved
  6. 2003 Medium

    Revealing that CEBPD protein has a short half-life (~120 min) and is degraded by ubiquitin-dependent nuclear proteasomal pathways during G0 explained how CEBPD protein levels are dynamically controlled despite ongoing transcription.

    Evidence Translation inhibitor chase, proteasome inhibitors, nuclear/cytoplasmic fractionation in mammary epithelial cells

    PMID:12554732

    Open questions at the time
    • E3 ubiquitin ligase responsible for CEBPD degradation not identified
    • Ubiquitination sites on CEBPD not mapped
  7. 2005 High

    Mapping a p38 MAPK docking site (aa 75–85) and a transactivation domain (aa 70–108) on CEBPD that are required for IL-1-dependent gene activation resolved how inflammatory signaling post-translationally enhances CEBPD transcriptional potency.

    Evidence Deletion mutagenesis, p38 inhibitor SB203580, reporter assays, Northern blot in hepatoma cells

    PMID:15694370

    Open questions at the time
    • Specific phosphorylation sites on CEBPD targeted by p38 not identified by mass spectrometry
    • Whether p38 phosphorylation alters CEBPD protein stability not tested
  8. 2008 High

    Discovering that SUMO1 modification at K120 converts CEBPD from a transcriptional activator to a repressor by recruiting HDAC1/3 (demonstrated at the PPARγ2 promoter) established a post-translational switch mechanism governing CEBPD's dual activator/repressor functions.

    Evidence SUMOylation mutant constructs, ChIP for HDAC1/3 recruitment, serial deletion and site-directed mutagenesis of PPARγ2 promoter

    PMID:18619497

    Open questions at the time
    • Signals that control the balance between sumoylated and non-sumoylated CEBPD unknown
    • Genome-wide identification of SUMO-dependent CEBPD repression targets not performed
  9. 2010 High

    A burst of studies in 2010 established multiple new CEBPD functions: transcriptional activation of CDC27/APC3 leading to cyclin D1 degradation (linking CEBPD to cell cycle control via the APC/C), direct transactivation of SOD1 conferring cisplatin resistance, regulation of TLR8 transcription, induction of PTX3 in neuroinflammation, and — critically — a transcription-independent scaffolding role bridging FANCD2 and importin 4 for DNA damage repair.

    Evidence CEBPD knockout MEFs, siRNA, ubiquitination assays for CDC27/cyclin D1; ChIP and ROS assays for SOD1; ChIP for TLR8; reciprocal Co-IP, nuclear import assays, and FANCD2 monoubiquitination readouts for the scaffolding function

    PMID:20385105 PMID:20439707 PMID:20805509 PMID:20829351 PMID:21112127

    Open questions at the time
    • Structural basis of the CEBPD–FANCD2–IPO4 ternary complex not determined
    • Relative importance of transcription-dependent vs. -independent CEBPD functions in DNA damage response unclear
    • Whether CEBPD scaffolding role extends to other Fanconi pathway substrates unknown
  10. 2011 High

    Identifying CEBPD as a repressor of prolactin expression through physical interaction with Pit1, and as a regulator of VEGF-C/VEGFR3-driven lymphangiogenesis via HIF-1α, expanded CEBPD's roles to endocrine regulation and tumor-associated vascular remodeling.

    Evidence ChIP, Co-IP of CEBPD–Pit1, reporter assays for PRL; CEBPD knockout mice showing reduced lymphangiogenesis and metastasis

    PMID:21666710 PMID:21980073

    Open questions at the time
    • CEBPD–Pit1 interaction interface not structurally resolved
    • Whether CEBPD-dependent lymphangiogenesis operates independently of its cell-cycle arrest functions unclear
  11. 2013 High

    Demonstrating that Miz1 terminates LPS-induced inflammation by recruiting HDAC1 to repress CEBPD transcription (dependent on Miz1 Ser178 phosphorylation) identified a key negative feedback mechanism that limits CEBPD-driven inflammatory gene expression.

    Evidence Miz1 POZ domain disruption in mice, Ser178 mutagenesis, HDAC1 ChIP at CEBPD promoter, cytokine measurements

    PMID:23525087

    Open questions at the time
    • Kinase responsible for Miz1 Ser178 phosphorylation not identified
    • Whether other C/EBP family members are similarly repressed by Miz1 not addressed
  12. 2016 High

    Showing that cisplatin induces CEBPD through the EGFR/STAT3 axis and that CEBPD directly activates ABCB1 and ABCC2 drug transporter genes established CEBPD as a mediator of chemotherapy cross-resistance, validated in xenograft models.

    Evidence ChIP at ABCB1/ABCC2 promoters, siRNA, EGFR/STAT3 inhibitors, xenograft assays in bladder carcinoma

    PMID:27435393

    Open questions at the time
    • Whether CEBPD-mediated drug resistance operates in tumor types beyond bladder carcinoma not tested
    • Contribution of CEBPD vs. other transcription factors to ABCB1 induction not quantified
  13. 2021 High

    Discovering that BRD4 controls CEBPD expression through bromodomain-1-dependent binding to an H3K27ac-marked enhancer, and that BRD4 and CEBPD physically interact and co-occupy the Cebpd locus, revealed an epigenetic feedforward loop governing CEBPD transcription that is pharmacologically targetable by JQ1.

    Evidence ChIP-seq, enhancer deletion, reciprocal Co-IP, bromodomain-specific constructs, JQ1 disruption

    PMID:33768129

    Open questions at the time
    • Whether the BRD4–CEBPD loop operates genome-wide at other CEBPD target genes not established
    • Contribution of BRD4 BD1 vs. BD2 at other C/EBP family gene loci unknown
  14. 2023 High

    Demonstrating that HIF1α/HIF2α activate the CEBPD promoter under hypoxia and that CEBPD directly binds and activates the FN1 promoter to drive EGFR/PI3K-mediated glioblastoma invasion established a hypoxia→CEBPD→FN1→integrin signaling axis in tumor progression.

    Evidence ChIP-seq, ChIP-qPCR, luciferase reporter, HIF overexpression, proteomic and Western blot analyses in glioblastoma cells

    PMID:37059730

    Open questions at the time
    • Whether the HIF–CEBPD–FN1 axis operates in non-CNS hypoxic tumors not tested
    • Relative contribution of HIF1α vs. HIF2α to CEBPD induction not quantified
  15. 2024 High

    Identifying CEBPD as a key downstream effector of IL-21 signaling in NK cells — where its deletion reduces cytotoxicity and metabolic fitness and its overexpression enhances long-term anti-tumor activity — placed CEBPD as a functional reprogramming factor in innate immune effector cells.

    Evidence CEBPD deletion and overexpression in NK cells, ATAC-seq, in vivo GBM models, cytotoxicity and metabolic assays

    PMID:39137729

    Open questions at the time
    • Direct transcriptional targets of CEBPD in NK cells not catalogued
    • Whether CEBPD operates similarly in other innate lymphoid cell subsets not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Despite extensive characterization of CEBPD's transcriptional targets and post-translational regulation, several core mechanistic questions remain: the E3 ligase(s) mediating CEBPD ubiquitin-dependent degradation, the structural basis of the CEBPD–FANCD2–IPO4 scaffolding complex, the genome-wide map of SUMO-dependent CEBPD repression targets, and the signals controlling the activator-to-repressor switch via SUMOylation are unresolved.
  • E3 ubiquitin ligase for CEBPD not identified
  • No structural model of CEBPD in any complex
  • Genome-wide SUMO-dependent repression targets not mapped
  • Integration of transcription-dependent and -independent CEBPD functions in DNA damage not modeled

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 11 GO:0003677 DNA binding 7 GO:0060090 molecular adaptor activity 1
Localization
GO:0005634 nucleus 4
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-73894 DNA Repair 2
Partners
ATF5BRD4CEBPBFANCD2HDAC1IPO4PIT1PU.1

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 CEBPD (NF-IL6β) forms a heterodimer with NF-IL6 (C/EBPβ) in vitro, and the heterodimeric complex binds the same DNA sequences as respective homodimers; CEBPD shows synergistic transcriptional activation with NF-IL6 in transient luciferase assays. In vitro heterodimerization assay, EMSA, transient luciferase reporter assay Proceedings of the National Academy of Sciences of the United States of America High 1741402
1993 CEBPD is the major IL-1-inducible protein that binds the C/EBP site in the C3 promoter and trans-activates the human complement C3 gene in an IL-1-responsive manner; CEBPD protein accumulates in the nucleus after IL-1 treatment of Hep3B cells. EMSA with supershift antibodies, Western immunoblot, co-transfection reporter assay Proceedings of the National Academy of Sciences of the United States of America High 8385337
1993 CEBPD (C/EBPδ/NF-IL6β) is transcriptionally induced by IL-6 in Hep3B hepatoma cells and constitutively activates transcription from IL-6 responsive elements (IL-6REs) in the promoters of hemopexin, haptoglobin, and CRP, unlike IL-6DBP/NF-IL6 whose activity is regulated post-translationally. Transient transfection reporter assay, Western blot of nuclear extracts Nucleic acids research High 7680115
1993 The human CEBPD gene is intronless and maps to the pericentromeric region of chromosome 8 (8q11), with its protein product binding CCAAT homology and viral enhancer core sequences. cDNA/genomic cloning, FISH, somatic cell hybrid mapping Genomics Medium 8314590
1995 CEBPD (NF-IL6β) physically interacts with PU.1 through its leucine zipper domain and the carboxyl-terminal 28 amino acids of PU.1 (Ets domain); the two proteins synergistically activate transcription and can simultaneously bind adjacent DNA sites without altering each other's DNA-binding kinetics. Far Western blot, cDNA library screen, EMSA, transient transfection synergy assay, deletion mutagenesis Journal of immunology High 7594592
1995 Growth hormone induces CEBPD at the transcriptional level (increased mRNA superinducible by cycloheximide) in 3T3-F442A preadipocytes, distinct from its translational activation of C/EBPβ; this induction is not observed with insulin. EMSA, Western blot, Northern blot, pharmacological inhibitors of JAK2 and protein kinase C Molecular endocrinology Medium 7760844
1996 VIP, PACAP, and noradrenaline induce CEBPD expression in cortical astrocytes via the cAMP second-messenger pathway; CEBPD behaves as a cAMP-inducible immediate-early gene, and forced expression of CEBPD enhances glycogen resynthesis in astrocytes. Northern blot, protein synthesis inhibitor assays, transfection with expression vectors measuring glycogen resynthesis The Journal of neuroscience High 8558260
1997 CEBPD expression is induced in mammary epithelial cells (COMMA D) arrested in G0 by serum/growth factor withdrawal or contact inhibition; antisense-mediated loss of CEBPD markedly delays growth arrest, establishing a role for CEBPD in G0 arrest. Northern blot, Western blot, EMSA, antisense construct transfection, BrdU incorporation The Journal of biological chemistry High 9045647
2000 CEBPD and C/EBPα transactivate the CYP2B1 promoter in lung epithelial cells; a proximal C/EBP-binding site in the CYP2B1 promoter is necessary for this transactivation, as shown by site-directed mutagenesis. Transient transfection reporter assay, EMSA, site-directed mutagenesis Molecular cell biology research communications Medium 10683316
2001 CEBPD is essential for the second (de novo protein synthesis-dependent) phase of LPS-induced COX-2 mRNA induction in macrophages; C/EBPβ-knockout macrophages are defective in both phases, and CEBPD synthesis is induced by LPS in a MAPK/SAPK2/p38-dependent manner. C/EBPβ-knockout macrophages, pharmacological inhibition of MAPK and p38 cascades, Northern blot, Western blot The Journal of biological chemistry High 11668179
2003 CEBPD protein levels are short-lived in G0-arrested mammary epithelial cells (t½ ~120 min); C/EBPδ protein is degraded in a ubiquitin-dependent manner, primarily in the nucleus, during G0 growth arrest. Protein half-life assays with translation inhibitors, ubiquitin-dependent proteasome inhibitor assays, nuclear/cytoplasmic fractionation The Journal of biological chemistry Medium 12554732
2005 IL-1β regulates CEBPD transcriptional activity through p38 MAP kinase; a docking site for p38 MAPK located between amino acids 75–85 is necessary for CEBPD phosphorylation, and a transactivation domain between amino acids 70–108 is required for IL-1-dependent haptoglobin induction and p300-dependent transactivation. p38 kinase inhibitor (SB203580), deletion mutagenesis, transient transfection reporter assay, Northern blot Biochemical and biophysical research communications High 15694370
2007 ΔNp63α represses CEBPD expression in keratinocytes; CEBPD in turn binds to and activates the ΔNp63 promoter, establishing a reciprocal regulatory loop; CEBPD is found on p63 target gene promoters in vivo by ChIP analysis. RNAi screening, RT-PCR, ChIP, reporter assay, overexpression and inactivation studies BMC molecular biology High 17903252
2008 CEBPD is sumoylated at lysine 120 by SUMO1; sumoylated CEBPD recruits HDAC1 and HDAC3 to the PPARG2 promoter to inactivate transcription, while non-sumoylated CEBPD acts as an activator; identified two CEBPD-binding motifs on the PPARG2 promoter at −324/−311 and −158/−145. 5'-serial deletion reporter analysis, site-directed mutagenesis of CEBPD binding sites, in vivo ChIP, sumoylation mutant constructs Biochimica et biophysica acta High 18619497
2010 CEBPD induces expression of the CDC27/APC3 subunit of the APC/C complex, leading to polyubiquitination and proteasomal degradation of cyclin D1; CEBPD also down-regulates cyclin B1, Skp2, and Plk-1; in CEBPD knockout MEFs, Cdc27 levels are reduced and cyclin D1 levels are elevated. CEBPD knockout MEF analysis, siRNA silencing, Western blot, co-immunoprecipitation/ubiquitination assays Proceedings of the National Academy of Sciences of the United States of America High 20439707
2010 CEBPD physically interacts with FANCD2 and importin 4 (IPO4) via separate domains, mediating FANCD2-IPO4 association and augmenting nuclear import of FANCD2; this promotes FANCD2 monoubiquitination required for DNA repair; this is a transcription-independent function of CEBPD. Co-immunoprecipitation, gene knockout, protein overexpression/depletion, nuclear import assays, FANCD2 monoubiquitination assays Proceedings of the National Academy of Sciences of the United States of America High 20805509
2010 CEBPD induces expression of PTX3 (pentraxin-3) in astrocytes, and PTX3 participates in attenuating macrophage-mediated phagocytosis of damaged neuron cells, establishing an astrocyte CEBPD→PTX3 axis in neuroinflammation. Global gene expression profiling, reporter assays, siRNA knockdown, phagocytosis functional assays Neurobiology of aging Medium 21112127
2010 CEBPD directly transactivates the SOD1 promoter, reducing cisplatin-induced reactive oxygen species and apoptosis in bladder carcinoma cells, conferring drug resistance. Reporter assay, ChIP, siRNA knockdown, ROS measurement, apoptosis assay Biochemical pharmacology Medium 20385105
2010 CEBPD and STAT-1 are required for basal and R848-stimulated transcriptional activity of the human TLR8 promoter; CEBPD binds three C/EBP cis-acting elements in the TLR8 promoter, with enhanced binding upon R848 stimulation. Luciferase reporter assay, ChIP assay The Journal of biological chemistry Medium 20829351
2011 CEBPD inhibits prolactin (PRL) expression by binding to the PRL promoter and suppressing PRL promoter activity (96% suppression); CEBPD physically interacts with Pit1 and attenuates each other's binding to the PRL promoter; CEBPD also suppresses c-Myc, survivin, and cyclins B1, B2, and D1 expression. ChIP, luciferase reporter assay, co-immunoprecipitation, siRNA knockdown, microarray gene expression profiling Molecular endocrinology High 21980073
2011 CEBPD regulates VEGF-C and VEGFR3 expression in lymphatic endothelial cells (LECs) to drive lymphangiogenesis; CEBPD expression is induced by hypoxia, and CEBPD regulates HIF-1α which in turn mediates VEGF-C and VEGFR3 upregulation; genetic deletion of CEBPD in mice reduces lymphangiogenesis and pulmonary metastases. CEBPD knockout mice, forced expression and knockdown in LECs, in vitro migration and network formation assays, Western blot, reporter assay Oncogene High 21666710
2012 CEBPD has anti-apoptotic and anti-inflammatory roles in pancreatic β-cells; CEBPD deficiency exacerbates cytokine-induced apoptosis through increased CHOP and BIM expression; CEBPD deficiency boosts chemokine production (CXCL1, 9, 10, CCL20) by hampering IRF-1 upregulation and increasing STAT1 activation. siRNA knockdown, double knockdown epistasis, overexpression, caspase cleavage assays, ELISA for chemokines PloS one High 22347430
2013 The transcription factor Miz1 terminates LPS-induced inflammation by repressing CEBPD transcription; after LPS stimulation, Miz1 is phosphorylated at Ser178, which is required for recruitment of HDAC1 to repress the CEBPD gene, thereby limiting proinflammatory cytokine expression. Genetic disruption of Miz1 POZ domain in mice, Miz1 Ser178 mutagenesis, HDAC1 co-immunoprecipitation/ChIP, cytokine measurement Nature immunology High 23525087
2016 CEBPD expression is induced by cisplatin through the EGFR/STAT3 pathway in bladder carcinoma cells; CEBPD then directly activates ABCB1 and ABCC2 drug transporter genes, conferring cross-resistance to paclitaxel; inhibition of EGFR or STAT3 reverses this resistance. siRNA loss-of-function, reporter assay, ChIP, xenograft animal assay, EGFR/STAT3 inhibitors Clinical cancer research High 27435393
2019 DN-ATF5 associates in cells with CEBPB and CEBPD (and CCDC6) via leucine zipper interactions, blocking formation of transcriptionally active CEBPB and CEBPD homodimers and heterodimers; CEBPB or CEBPD knockdown promotes apoptosis in cancer cells but not normal astrocytes. Unbiased pull-down with mass spectrometry, immunoblotting, siRNA knockdown, transcriptional activity assays Molecular cancer research High 31676720
2020 IPO4 (importin 4) augments nuclear translocation of CEBPD through nuclear localization signals (NLS); nuclear CEBPD then transcriptionally upregulates PRKDC (DNA-PKcs), activating DNA damage repair; cisplatin treatment strengthens CEBPD transcriptional activity toward PRKDC. shRNA knockdown, reporter assay, nuclear fractionation, in vivo xenograft, loss-of-function assays in cervical cancer cells Oncogene Medium 32661323
2020 SUMOylation of PUM2 (by UBE2I/SUMO2/3) decreases the ability of PUM2 to inhibit CEBPD mRNA stability; elevated CEBPD then binds the DSG2 promoter to upregulate DSG2, promoting vasculogenic mimicry in glioma cells. Co-IP, immunofluorescence, RNA immunoprecipitation (RIP), ChIP, luciferase assay, 3D cell culture VM assay Clinical and translational medicine Medium 32997416
2021 BRD4 controls CEBPD expression via its bromodomain-1 (not bromodomain-2) by binding a H3K27ac-marked enhancer at the Cebpd locus; BRD4 and CEBPD proteins physically co-immunoprecipitate and co-occupy the Cebpd promoter and enhancer DNA, forming a BRD4/CEBPD/promoter/enhancer complex that is disrupted by JQ1. ChIP-seq, genomic enhancer deletion, siRNA silencing, reciprocal Co-IP, BRD4 bromodomain-specific constructs Molecular therapy. Methods & clinical development High 33768129
2021 Deletion of the CEBPD transactivation domain (ΔTAD) reveals that the context-dependent role of CEBPD in macrophage cytokine production depends on compensatory transcriptional activity; CRISPR-generated ΔTAD macrophages reveal a large discrepancy between transcriptional programs in CEBPD knockout vs. CEBPD-ΔTAD macrophages. CRISPR-Cas9 endogenous TAD deletion, RNA-seq comparison of KO vs. ΔTAD macrophages, LPS stimulation assays Cells Medium 34571881
2023 In glioblastoma, HIF1α and HIF2α activate the CEBPD promoter under hypoxia; CEBPD in turn directly binds and activates the FN1 (fibronectin) promoter; FN1 and its integrin receptors mediate CEBPD-induced EGFR phosphorylation and PI3K pathway activation, promoting invasion. Proteomic analysis, TF binding analysis, HIF1α/HIF2α overexpression, ChIP-qPCR/ChIP-seq, luciferase reporter assay, Western blot Cell death & disease High 37059730
2024 CEBPD acts as a key transcription factor in IL-21-engineered NK cells; deletion of CEBPD reduces IL-21 NK cell cytotoxicity and metabolic fitness, while overexpression enhances long-term anti-tumor activity, placing CEBPD downstream of IL-21 signaling in NK cell functional reprogramming. CEBPD deletion and overexpression in NK cells, chromatin accessibility (ATAC-seq), in vivo GBM models, cytotoxicity and metabolic assays Cancer cell High 39137729

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 A postnatal switch of CELF and MBNL proteins reprograms alternative splicing in the developing heart. Proceedings of the National Academy of Sciences of the United States of America 426 19075228
2001 The CELF family of RNA binding proteins is implicated in cell-specific and developmentally regulated alternative splicing. Molecular and cellular biology 368 11158314
1992 A member of the C/EBP family, NF-IL6 beta, forms a heterodimer and transcriptionally synergizes with NF-IL6. Proceedings of the National Academy of Sciences of the United States of America 313 1741402
2011 The importance of CELF control: molecular and biological roles of the CUG-BP, Elav-like family of RNA-binding proteins. Wiley interdisciplinary reviews. RNA 194 22180311
2015 Antagonistic regulation of mRNA expression and splicing by CELF and MBNL proteins. Genome research 161 25883322
1993 The two C/EBP isoforms, IL-6DBP/NF-IL6 and C/EBP delta/NF-IL6 beta, are induced by IL-6 to promote acute phase gene transcription via different mechanisms. Nucleic acids research 161 7680115
2010 Induction of neutrophil gelatinase-associated lipocalin expression by co-stimulation with interleukin-17 and tumor necrosis factor-alpha is controlled by IkappaB-zeta but neither by C/EBP-beta nor C/EBP-delta. The Journal of biological chemistry 133 20220144
1993 Participation of the transcription factor C/EBP delta in the acute-phase regulation of the human gene for complement component C3. Proceedings of the National Academy of Sciences of the United States of America 132 8385337
2005 Mammalian CELF/Bruno-like RNA-binding proteins: molecular characteristics and biological functions. Biochimie 127 16480813
2001 The induction of cyclooxygenase-2 mRNA in macrophages is biphasic and requires both CCAAT enhancer-binding protein beta (C/EBP beta ) and C/EBP delta transcription factors. The Journal of biological chemistry 124 11668179
1997 The processive endocellulase CelF, a major component of the Clostridium cellulolyticum cellulosome: purification and characterization of the recombinant form. Journal of bacteriology 113 8981979
1995 Multiple proteins physically interact with PU.1. Transcriptional synergy with NF-IL6 beta (C/EBP delta, CRP3). Journal of immunology (Baltimore, Md. : 1950) 95 7594592
2003 Antagonistic regulation of alpha-actinin alternative splicing by CELF proteins and polypyrimidine tract binding protein. RNA (New York, N.Y.) 92 12649496
1996 Vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide, and noradrenaline induce the transcription factors CCAAT/enhancer binding protein (C/EBP)-beta and C/EBP delta in mouse cortical astrocytes: involvement in cAMP-regulated glycogen metabolism. The Journal of neuroscience : the official journal of the Society for Neuroscience 90 8558260
1995 Early responses of trans-activating factors to growth hormone in preadipocytes: differential regulation of CCAAT enhancer-binding protein-beta (C/EBP beta) and C/EBP delta. Molecular endocrinology (Baltimore, Md.) 81 7760844
2009 MBNL and CELF proteins regulate alternative splicing of the skeletal muscle chloride channel CLCN1. Nucleic acids research 80 19720736
2004 CELF6, a member of the CELF family of RNA-binding proteins, regulates muscle-specific splicing enhancer-dependent alternative splicing. The Journal of biological chemistry 77 14761971
1997 CCAAT/enhancer-binding protein-delta (C/EBP-delta) is induced in growth-arrested mouse mammary epithelial cells. The Journal of biological chemistry 76 9045647
2010 CCAAT/enhancer binding protein delta (CEBPD) elevating PTX3 expression inhibits macrophage-mediated phagocytosis of dying neuron cells. Neurobiology of aging 73 21112127
2013 Suppression of inflammation and acute lung injury by Miz1 via repression of C/EBP-δ. Nature immunology 71 23525087
2008 Posttranscriptional regulation of gene networks by GU-rich elements and CELF proteins. RNA biology 70 18971639
2005 Cardiac tissue-specific repression of CELF activity disrupts alternative splicing and causes cardiomyopathy. Molecular and cellular biology 68 15988035
2011 C/EBP-δ regulates VEGF-C autocrine signaling in lymphangiogenesis and metastasis of lung cancer through HIF-1α. Oncogene 67 21666710
2010 C/EBP{delta} targets cyclin D1 for proteasome-mediated degradation via induction of CDC27/APC3 expression. Proceedings of the National Academy of Sciences of the United States of America 65 20439707
2024 Interleukin-21 engineering enhances NK cell activity against glioblastoma via CEBPD. Cancer cell 62 39137729
2012 CUG-BP, Elav-like family (CELF)-mediated alternative splicing regulation in the brain during health and disease. Molecular and cellular neurosciences 60 23247071
2003 Keratinocyte growth factor and the transcription factors C/EBP alpha, C/EBP delta, and SREBP-1c regulate fatty acid synthesis in alveolar type II cells. The Journal of clinical investigation 58 12865412
2017 Metformin promotes apoptosis in hepatocellular carcinoma through the CEBPD-induced autophagy pathway. Oncotarget 57 28099155
2010 Transcriptional up-regulation of SOD1 by CEBPD: a potential target for cisplatin resistant human urothelial carcinoma cells. Biochemical pharmacology 57 20385105
2016 Inhibition of the EGFR/STAT3/CEBPD Axis Reverses Cisplatin Cross-resistance with Paclitaxel in the Urothelial Carcinoma of the Urinary Bladder. Clinical cancer research : an official journal of the American Association for Cancer Research 55 27435393
2012 The transcription factor C/EBP delta has anti-apoptotic and anti-inflammatory roles in pancreatic beta cells. PloS one 54 22347430
2023 CEBPD is a master transcriptional factor for hypoxia regulated proteins in glioblastoma and augments hypoxia induced invasion through extracellular matrix-integrin mediated EGFR/PI3K pathway. Cell death & disease 52 37059730
2002 C/EBP-beta, C/EBP-delta, PU.1, AML1 genes: mutational analysis in 381 samples of hematopoietic and solid malignancies. Leukemia research 50 11916518
2017 Ancient antagonism between CELF and RBFOX families tunes mRNA splicing outcomes. Genome research 49 28512194
2013 Position-dependent and neuron-specific splicing regulation by the CELF family RNA-binding protein UNC-75 in Caenorhabditis elegans. Nucleic acids research 47 23416545
2016 Conserved functional antagonism of CELF and MBNL proteins controls stem cell-specific alternative splicing in planarians. eLife 46 27502555
2008 HDAC1/HDAC3 modulates PPARG2 transcription through the sumoylated CEBPD in hepatic lipogenesis. Biochimica et biophysica acta 46 18619497
1999 Cellobiose-6-phosphate hydrolase (CelF) of Escherichia coli: characterization and assignment to the unusual family 4 of glycosylhydrolases. Journal of bacteriology 46 10572139
2010 CEBPD reverses RB/E2F1-mediated gene repression and participates in HMDB-induced apoptosis of cancer cells. Clinical cancer research : an official journal of the American Association for Cancer Research 44 20971808
2005 Identification of CELF splicing activation and repression domains in vivo. Nucleic acids research 41 15894795
1996 Molecular study and overexpression of the Clostridium cellulolyticum celF cellulase gene in Escherichia coli. Microbiology (Reading, England) 40 8936327
2013 CELF family RNA-binding protein UNC-75 regulates two sets of mutually exclusive exons of the unc-32 gene in neuron-specific manners in Caenorhabditis elegans. PLoS genetics 39 23468662
1996 Effect of thermal injury on the expression of transcription factors that regulate acute phase response genes: the response of C/EBP alpha, C/EBP beta, and C/EBP delta to thermal injury. Surgery 38 8650608
2019 Dominant-Negative ATF5 Compromises Cancer Cell Survival by Targeting CEBPB and CEBPD. Molecular cancer research : MCR 37 31676720
2010 The role of CELF proteins in neurological disorders. RNA biology 36 20622515
2010 CCAAT/enhancer binding protein delta (C/EBPdelta, CEBPD)-mediated nuclear import of FANCD2 by IPO4 augments cellular response to DNA damage. Proceedings of the National Academy of Sciences of the United States of America 35 20805509
2020 SUMOylation of PUM2 promotes the vasculogenic mimicry of glioma cells via regulating CEBPD. Clinical and translational medicine 33 32997416
1991 Nucleotide sequence of the cellulase gene celF of Clostridium thermocellum. Research in microbiology 33 1805307
2009 The neurofibromatosis type I pre-mRNA is a novel target of CELF protein-mediated splicing regulation. Nucleic acids research 32 19854948
1993 The human C/EBP delta (CRP3/CELF) gene: structure and chromosomal localization. Genomics 32 8314590
2015 ROCK2 promotes HCC proliferation by CEBPD inhibition through phospho-GSK3β/β-catenin signaling. FEBS letters 31 25771860
2011 The CCAAT/enhancer binding protein (C/EBP) δ is differently regulated by fibrillar and oligomeric forms of the Alzheimer amyloid-β peptide. Journal of neuroinflammation 31 21492414
2010 C/EBP{delta} and STAT-1 are required for TLR8 transcriptional activity. The Journal of biological chemistry 31 20829351
2020 Inhibiting Importin 4-mediated nuclear import of CEBPD enhances chemosensitivity by repression of PRKDC-driven DNA damage repair in cervical cancer. Oncogene 30 32661323
2018 Transcription factors Tp73, Cebpd, Pax6, and Spi1 rather than DNA methylation regulate chronic transcriptomics changes after experimental traumatic brain injury. Acta neuropathologica communications 30 29482641
2016 CELF RNA binding proteins promote axon regeneration in C. elegans and mammals through alternative splicing of Syntaxins. eLife 30 27253061
2016 MiR-193b Mediates CEBPD-Induced Cisplatin Sensitization Through Targeting ETS1 and Cyclin D1 in Human Urothelial Carcinoma Cells. Journal of cellular biochemistry 30 27918099
2021 Fibroblast CEBPD/SDF4 axis in response to chemotherapy-induced angiogenesis through CXCR4. Cell death discovery 29 33953165
2021 CELF Family Proteins in Cancer: Highlights on the RNA-Binding Protein/Noncoding RNA Regulatory Axis. International journal of molecular sciences 29 34681716
2015 Multiple Protein Kinases via Activation of Transcription Factors NF-κB, AP-1 and C/EBP-δ Regulate the IL-6/IL-8 Production by HIV-1 Vpr in Astrocytes. PloS one 29 26270987
2021 Cell-Penetrating CEBPB and CEBPD Leucine Zipper Decoys as Broadly Acting Anti-Cancer Agents. Cancers 28 34065488
2012 Artemisinic acid is a regulator of adipocyte differentiation and C/EBP δ expression. Journal of cellular biochemistry 28 22396222
2010 CELF proteins regulate CFTR pre-mRNA splicing: essential role of the divergent domain of ETR-3. Nucleic acids research 27 20631008
2007 Cloning and embryonic expression patterns of the chicken CELF family. Developmental dynamics : an official publication of the American Association of Anatomists 27 17584860
1996 Nuclear factor kappa B (NF-kappa B), nuclear factor interleukin-6 (NFIL-6 or C/EBP beta) and nuclear factor interleukin-6 beta (NFIL6-beta or C/EBP delta) are not sufficient to activate the endogenous interleukin-6 gene in the human breast carcinoma cell line MCF-7. Comparative analysis with MDA-MB-231 cells, an interleukin-6-expressing human breast carcinoma cell line. European journal of biochemistry 27 8774705
1995 Mouse chromosomal location of the CCAAT/enhancer binding proteins C/EBP beta (Cebpb), C/EBP delta (Cebpd), and CRP1 (Cebpe). Genomics 27 8530045
2007 Reciprocal regulation of p63 by C/EBP delta in human keratinocytes. BMC molecular biology 26 17903252
2003 Posttranscriptional and posttranslational regulation of C/EBP delta in G0 growth-arrested mammary epithelial cells. The Journal of biological chemistry 26 12554732
2014 The combination of the prodrugs perforin-CEBPD and perforin-granzyme B efficiently enhances the activation of caspase signaling and kills prostate cancer. Cell death & disease 25 24810056
2014 ABLIM1 splicing is abnormal in skeletal muscle of patients with DM1 and regulated by MBNL, CELF and PTBP1. Genes to cells : devoted to molecular & cellular mechanisms 25 25403273
2005 IL-1 beta-dependent regulation of C/EBP delta transcriptional activity. Biochemical and biophysical research communications 23 15694370
2021 A hierarchical and collaborative BRD4/CEBPD partnership governs vascular smooth muscle cell inflammation. Molecular therapy. Methods & clinical development 22 33768129
2021 CEBPD Potentiates the Macrophage Inflammatory Response but CEBPD Knock-Out Macrophages Fail to Identify CEBPD-Dependent Pro-Inflammatory Transcriptional Programs. Cells 22 34571881
2020 Shikonin inhibits CEBPD downregulation in IL‑17‑treated HaCaT cells and in an imiquimod‑induced psoriasis model. Molecular medicine reports 22 32705251
2009 C/EBP beta and C/EBP delta expression is elevated in the early phase of ethanol-induced hepatosteatosis in mice. Acta pharmacologica Sinica 22 19617893
2023 Targeting Transcription Factors ATF5, CEBPB and CEBPD with Cell-Penetrating Peptides to Treat Brain and Other Cancers. Cells 21 36831248
2021 Exosomal microRNA let-7-5p from Taenia pisiformis Cysticercus Prompted Macrophage to M2 Polarization through Inhibiting the Expression of C/EBP δ. Microorganisms 21 34209741
2010 Differential expression of the Brunol/CELF family genes during Xenopus laevis early development. The International journal of developmental biology 21 19757395
2003 Expression pattern of the CCAAT/enhancer-binding proteins C/EBP-alpha, C/EBP-beta and C/EBP-delta in the human placenta. Virchows Archiv : an international journal of pathology 21 14691721
2012 Repression of nuclear CELF activity can rescue CELF-regulated alternative splicing defects in skeletal muscle models of myotonic dystrophy. PLoS currents 20 22453899
2011 CEBPD suppresses prolactin expression and prolactinoma cell proliferation. Molecular endocrinology (Baltimore, Md.) 20 21980073
2007 Expression of MBNL and CELF mRNA transcripts in muscles with myotonic dystrophy. Neuromuscular disorders : NMD 20 17331722
2007 The Cebpd (C/EBPdelta) gene is induced by luteinizing hormones in ovarian theca and interstitial cells but is not essential for mouse ovary function. PloS one 20 18092000
2018 Gemcabene, a first-in-class lipid-lowering agent in late-stage development, down-regulates acute-phase C-reactive protein via C/EBP-δ-mediated transcriptional mechanism. Molecular and cellular biochemistry 18 29644527
2010 CCAAT/Enhancer Binding Protein-delta (C/EBP-delta) regulates cell growth, migration and differentiation. Cancer cell international 18 21143913
2009 Induction of CRP3/MLP expression during vein arterialization is dependent on stretch rather than shear stress. Cardiovascular research 18 19351738
2000 CYP2B1 is regulated by C/EBP alpha and C/EBP delta inlung epithelial cells. Molecular cell biology research communications : MCBRC 18 10683316
1998 Crystallization of the catalytic domain of Clostridium cellulolyticum CeLF cellulase in the presence of a newly synthesized cellulase inhibitor. Acta crystallographica. Section D, Biological crystallography 18 9761829
2020 MiR-324-5p/PTPRD/CEBPD axis promotes papillary thyroid carcinoma progression via microenvironment alteration. Cancer biology & therapy 17 32151175
2008 CELF-mediated alternative splicing is required for cardiac function during early, but not later, postnatal life. Journal of molecular and cellular cardiology 17 19073192
1999 Local signals induce CCAAT/enhancer binding protein-delta (C/EBP-delta) and C/EBP-beta mRNA expression in the involuting mouse mammary gland. Breast cancer research and treatment 17 10634518
2018 Cebpd Is Essential for Gamma-Tocotrienol Mediated Protection against Radiation-Induced Hematopoietic and Intestinal Injury. Antioxidants (Basel, Switzerland) 16 29642403
2017 C/EBP-δ positively regulates MDSC expansion and endothelial VEGFR2 expression in tumor development. Oncotarget 16 28881585
2003 CelF of Orpinomyces PC-2 has an intron and encodes a cellulase (CelF) containing a carbohydrate-binding module. Applied biochemistry and biotechnology 16 12721415
2011 Expression of a dominant negative CELF protein in vivo leads to altered muscle organization, fiber size, and subtype. PloS one 15 21541285
2024 The role of CELF family in neurodevelopment and neurodevelopmental disorders. Neurobiology of disease 14 38729272
2022 Angiogenesis Driven by the CEBPD-hsa-miR-429-VEGFA Signaling Axis Promotes Urothelial Carcinoma Progression. Cells 14 35203290
2021 Biological significance of MYC and CEBPD coamplification in urothelial carcinoma: Multilayered genomic, transcriptional and posttranscriptional positive feedback loops enhance oncogenic glycolysis. Clinical and translational medicine 14 34954904
2021 High-Throughput Screening for CEBPD-Modulating Compounds in THP-1-Derived Reporter Macrophages Identifies Anti-Inflammatory HDAC and BET Inhibitors. International journal of molecular sciences 13 33809617
2010 Inhibition of LPS-induced C/EBP delta by trichostatin A has a positive effect on LPS-induced cyclooxygenase 2 expression in RAW264.7 cells. Journal of cellular biochemistry 13 20506344