Affinage

CREB1

Cyclic AMP-responsive element-binding protein 1 · UniProt P16220

Length
327 aa
Mass
35.1 kDa
Annotated
2026-06-09
100 papers in source corpus 33 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CREB1 is a nuclear phosphoprotein transcription factor that integrates multiple upstream signaling cascades to drive transcription of cAMP-responsive target genes, functioning as a central, signal-convergent regulator of cellular proliferation, differentiation, energy homeostasis, and stress responses (PMID:2142119, PMID:25084773). Its activity is gated by phosphorylation: PKA downstream of cAMP/AKIP1 (PMID:35474062), CDK5 in a PKA-independent manner (PMID:29742423), CaMKIV downstream of DJ-1/CaMKKβ (PMID:31232473), PI3K/AKT and RSK pathways (PMID:25084773, PMID:26348925), S6K1 downstream of HTR2B/Akt/mTOR (which drives Ser133 phosphorylation and nuclear translocation) (PMID:38381131), and p38 MAPK (PMID:33753566). Once activated, CREB1 binds CRE elements (including CREB half-sites such as GTCA) in target promoters and recruits co-activators — it cooperates with CRTC1/CRTC2 (PMID:18758446, PMID:40069788), with the CBP/p300 histone acetyltransferases via the Lyl1 interaction (PMID:18160048), and with sequence-specific partners including SMAD3, MeCP2, PGR, and FoxO1 to activate context-specific programs (PMID:25084773, PMID:23493374, PMID:37786383, PMID:35562411). Through these mechanisms CREB1 directly transactivates a broad target repertoire including TGFB2, SCD, HLA-E, ZEB1, Lin28/VASP, SRGN, the lncRNAs CCAT1 and PVT1, and numerous miRNAs (miR-320a, miR-373, miR-922, miR-93-3p), thereby controlling tumor cell proliferation, migration, EMT, ferroptosis resistance, immune evasion, and viral replication (PMID:25084773, PMID:37957645, PMID:38902472, PMID:38381131, PMID:31754343, PMID:35696016, PMID:33786634). CREB1 output is restrained by CCDC6, which recruits HDAC1 and PP1 to CRE sites (PMID:20498639), and CREB1 levels are set post-translationally by Cullin-5-mediated ubiquitylation and degradation (PMID:36662868) and post-transcriptionally by Mettl3-dependent m6A stabilization of its mRNA (PMID:37267102). In the nervous system CREB1 governs long-term memory and neuronal reprogramming and modulates psychostimulant sensitivity, with CREM providing partial functional redundancy (PMID:31413073, PMID:38389831, PMID:21766169).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1990 High

    Established CREB1 as a discrete genomic locus and identified it as a nuclear phosphoprotein regulating cAMP-inducible transcription, providing the foundational identity of the gene.

    Evidence Somatic cell hybrid Southern blot and in situ hybridization mapping to chromosome 2q32.3-q34

    PMID:2142119

    Open questions at the time
    • No mechanistic detail of target genes or co-activator recruitment at this stage
    • Phosphorylation sites not yet mapped
  2. 2007 High

    Resolved how CREB1 can activate transcription independent of Ser133 phosphorylation, showing a partner protein bridges CREB1 to histone acetyltransferases.

    Evidence Co-IP with domain mapping, genome-wide ChIP-chip and reporter assays identifying Lyl1 recruitment of p300/CBP to CREB1 targets

    PMID:18160048

    Open questions at the time
    • Generality of phosphorylation-independent activation across other partners unknown
    • Physiological contexts limited to mapped targets (Id1, Id3, cyclin D3, etc.)
  3. 2008 High

    Defined the CREB1-CRTC1 module as the effector of leptin signaling in the hypothalamus, linking CREB1 to whole-body energy balance and fertility.

    Evidence Dominant-negative CREB1, hypothalamic ChIP of CRTC1 at Cartpt/Kiss1 promoters, Crtc1 KO mouse

    PMID:18758446

    Open questions at the time
    • Does not address CREB1 phosphorylation requirement in this context
    • CRTC1 dephosphorylation mechanism not fully resolved
  4. 2010 High

    Identified a direct repressor of CREB1, showing transcriptional output is actively restrained at CRE sites and that loss of this brake drives oncogenic CREB1 activity.

    Evidence Reciprocal Co-IP, ChIP and reporter assays showing CCDC6 recruits HDAC1/PP1 to CRE promoters; PTC tumor validation

    PMID:20498639

    Open questions at the time
    • Whether CCDC6 acts on all CREB1 targets or a subset unknown
    • Dynamics of repression versus activation switching not defined
  5. 2011 Medium

    Established that CREB1 functions in feedback miRNA loops and that striatal CREB1 modulates behavior, with CREM compensation revealing functional redundancy.

    Evidence ChIP of CREB1 at miRNA regulatory regions in thyroid cells (TSH loop); conditional striatal CREB1/CBP KO with behavioral assays

    PMID:21766169 PMID:21816899

    Open questions at the time
    • Extent of CREM redundancy across tissues unquantified
    • Direct versus indirect miRNA suppression mechanism incomplete
  6. 2013 Medium

    Placed CREB1 within the mTOR/autophagy axis and showed it cooperates with methyl-CpG-binding machinery, expanding its mechanistic repertoire to methylation-dependent transactivation and DNA-damage responses.

    Evidence siRNA epistasis in TSC2/PTEN-loss models with etoposide (mTOR axis); sequential ChIP and Co-IP with MeCP2 at the methylated Glut3 promoter

    PMID:23493374 PMID:24189100

    Open questions at the time
    • How mTOR mechanistically activates CREB1 not defined
    • Generality of CREB1-MeCP2 cooperation beyond Glut3 unknown
  7. 2014 High

    Demonstrated CREB1 cooperates with SMAD3 to drive an autocrine TGFB2 loop, integrating PI3K/AKT and RSK inputs into a defined oncogenic transcriptional output.

    Evidence ChIP of CREB1 at the TGFB2 promoter, pathway inhibitor epistasis, patient-derived glioblastoma xenografts

    PMID:25084773

    Open questions at the time
    • Structural basis of CREB1-SMAD3 cooperation not resolved
    • Relative contribution of AKT versus RSK phosphorylation unclear
  8. 2015 Medium

    Connected CREB1 to specific receptor-driven proliferation and to mitophagy, broadening its role across estrogen signaling and metabolic/organelle quality-control programs.

    Evidence ERα structure-function mutagenesis with PI3K/AKT inhibition and CREB1 reporters (E2 proliferation); promoter mapping and ChIP of CREB1 at miR-320a controlling VDAC1/mitophagy

    PMID:26348925 PMID:26472185

    Open questions at the time
    • Single-lab evidence for each axis
    • Direct CREB1 kinase in the ERα context not pinned down
  9. 2018 Medium

    Identified phosphorylation-independent and epigenetic kinase inputs to CREB1, showing CDK5 and SETD2/H3K36me3-supported ERK signaling sustain CREB1 activity in cancer.

    Evidence Drosophila suppressor screen with CDK5 inhibition in glioma stem cells; SETD2 mutant expression and CREB1 siQ in NSCLC with H3K36me3/pCREB1 readouts

    PMID:29742423 PMID:30093630

    Open questions at the time
    • Direct versus indirect CDK5 phosphorylation of CREB1 not shown biochemically
    • Mechanistic link from H3K36me3 to CREB1 phosphorylation incomplete
  10. 2019 Medium

    Linked CREB1 to CaMKIV-dependent neuronal gene control and defined isoform- and residue-specific requirements for its memory function, distinguishing roles from innate behavior.

    Evidence DJ-1/CaMKKβ Co-IP and Dj-1 KO mice (TH regulation); C. elegans CRH-1e isoform-specific KO, neuron-specific rescue and K247/K266 mutagenesis (LTM); ChIP of CREB1 at Lin28/VASP

    PMID:31232473 PMID:31413073 PMID:31754343

    Open questions at the time
    • Functional roles of K247/K266 residues mechanistically undefined
    • Conservation of isoform specialization in mammals untested
  11. 2021 Medium

    Established CREB1 as a constitutive driver of lineage differentiation and an immune-evasion factor, and showed coactivator competition (CREB1 vs p65 for CBP/p300) shapes pathway crosstalk.

    Evidence RNA-Seq and CREB1 inhibition in prostate luminal cells (ING4/JFK); CRISPR KO with pathway profiling and ChIP of CCAT1 (colorectal); ChIP at HLA-E with NK cytotoxicity assays (myeloma)

    PMID:33846571 PMID:35696016 PMID:38902472

    Open questions at the time
    • Mechanism setting constitutive CREB1 activity in luminal cells beyond PTEN loss unclear
    • Quantitative basis of coactivator competition not defined
  12. 2022 High

    Mapped CREB1 to additional disease programs — viral replication, macrophage polarization, and fibrosis — demonstrating its recruitment into viral structures and p38-driven activity.

    Evidence EBOV VP35-AKIP1 Co-IP, confocal colocalization in viral inclusion bodies, PKA-CREB1 inhibition; p38/Creb1/Klf4 ChIP in macrophages; ChIP of CREB1 at PVT1 in cardiac fibroblasts

    PMID:33753566 PMID:35063587 PMID:35474062

    Open questions at the time
    • Function of CREB1 within viral ribonucleoprotein complexes mechanistically unresolved
    • Direct DNA-binding role versus signaling role in VIBs not separated
  13. 2023 High

    Defined the post-translational and post-transcriptional control layers governing CREB1 abundance and extended its target repertoire to lipid metabolism and immune modulation.

    Evidence In vivo ubiquitylation assay and genetic screens (Cullin-5 degrades CREB1, CREB1-CCL2 axis); conditional Mettl3/Creb1 KO with m6A mapping and rescue (iNKT); ChIP/luciferase of SCD with rescue (ferroptosis); PGR/CREB1 EMSA/ChIP at PTPN11 (decidualization)

    PMID:36662868 PMID:37267102 PMID:37786383 PMID:37957645

    Open questions at the time
    • Stress signals triggering Cullin-5-mediated degradation incompletely defined
    • m6A reader linking Mettl3 to Creb1 mRNA stability not identified
  14. 2024 Medium

    Connected CREB1 to receptor-driven EMT/metastasis, neuroendocrine differentiation, and neuronal reprogramming, reinforcing its role as a convergent effector across signaling-to-fate programs.

    Evidence HTR2B/S6K1 axis with ChIP of pCREB1 at ZEB1 and metastasis models; CREB1/EZH2/REST rescue experiments in prostate NED; forskolin cAMP-CREB1-JNK reprogramming with electrophysiology

    PMID:38381131 PMID:38389831 PMID:38777812

    Open questions at the time
    • Mechanism by which CREB1 enhances EZH2 activity not biochemically resolved
    • Direct versus indirect repression of REST by CREB1 not separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many converging kinase inputs, coactivator/repressor competitions, and post-translational/RNA controls are integrated to specify which CREB1 target program is activated in a given cell type remains unresolved.
  • No unified model for context-specific target selection
  • Quantitative interplay of CRTC, CBP/p300, CCDC6, and partner TFs at single promoters undefined
  • Genome-wide phospho-form-resolved occupancy maps lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 10 GO:0003677 DNA binding 8
Localization
GO:0005654 nucleoplasm 4 GO:0005634 nucleus 2
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-74160 Gene expression (Transcription) 7 R-HSA-1643685 Disease 6
Partners
CCDC6CREBBPCRTC1CRTC2EP300MECP2PGRSMAD3

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 Crtc1 (CREB-regulated transcription coactivator-1) is required for Creb1-dependent transcriptional activation of Cartpt and Kiss1 genes in the hypothalamus. Leptin promotes nuclear dephosphorylation of Crtc1, which then co-occupies Cartpt and Kiss1 promoters with Creb1; a dominant-negative Creb1 polypeptide disrupted these effects, establishing Creb1-Crtc1 as the pathway mediating leptin's central effects on energy balance and fertility. Dominant-negative CREB1 expression, ChIP (chromatin immunoprecipitation) of hypothalamic Crtc1 at target promoters, Crtc1 overexpression/depletion in hypothalamic cells, Crtc1−/− mouse model Nature medicine High 18758446
2010 CCDC6 physically interacts with CREB1 and represses its transcriptional activity by recruiting histone deacetylase 1 (HDAC1) and protein phosphatase 1 (PP1) to CRE-containing promoters of CREB1 target genes (including AREG and cyclin A). Loss of CCDC6 via RET/PTC1 fusion leads to increased CREB1 phosphorylation and target gene expression in papillary thyroid carcinoma. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), reporter assays, expression analysis in PTC tumor specimens Oncogene High 20498639
2013 Creb1 forms a complex with Mecp2 at methylated CpG sites in the Glut3 gene promoter to transactivate neuronal Glut3 expression. Sequential ChIP showed Creb1 recruitment of Mecp2 to glut3-mCpGs; co-IP confirmed Creb1-Mecp2 association; siRNA depletion of Creb1 or Mecp2 reduced Glut3 expression, establishing a methylation-dependent transactivation mechanism. Sequential chromatin immunoprecipitation (ChIP), co-immunoprecipitation, siRNA knockdown, luciferase reporter assay, bisulfite sequencing Endocrinology High 23493374
2013 MTOR positively regulates CREB1 activity; impaired autophagy (due to TSC2 or PTEN loss) leads to CREB1 hyperactivation; CREB1 in turn promotes DNA damage and apoptosis in response to etoposide. Silencing Creb1 with siRNA protected MTOR-hyperactive cells from DNA damage-induced apoptosis, placing CREB1 downstream of MTOR and upstream of DNA damage responses. siRNA knockdown of Creb1, TSC2/PTEN loss-of-function models (MEFs and cancer lines), etoposide treatment, autophagy manipulation, analysis in TSC patient kidney tumor tissue and hepatocyte-specific PTEN-KO mouse livers Autophagy Medium 24189100
2014 CREB1 directly binds the TGFB2 gene promoter in cooperation with SMAD3 to mediate TGFβ-induced TGFβ2 transcription, creating an autocrine loop. The PI3K-AKT and RSK pathways regulate this loop through CREB1. Patient-derived glioblastoma in vivo models confirmed that CREB1 levels determine TGFβ2 expression. ChIP (CREB1 binding at TGFB2 promoter), dominant-negative and overexpression constructs, PI3K/AKT/RSK pathway inhibitors, patient-derived glioblastoma xenograft models Cancer discovery High 25084773
2007 CREB1 interacts with the transcription factor Lyl1 via the N-terminal domain of Lyl1 and the Q2 and KID domains of CREB1; this interaction recruits histone acetyltransferases p300 and CBP to CREB1-target promoters (including Id1, Id3, cyclin D3, Brca1, Btg2, Egr1) in the absence of CREB1 Ser133 phosphorylation, resulting in transcriptional activation. Co-immunoprecipitation, domain mapping, ChIP-chip (genome-wide promoter occupancy), reporter assays Biochimica et biophysica acta High 18160048
2015 CREB1 binds the promoter of miR-320a and activates its transcription during serum starvation; this induces mitophagy by downregulating VDAC1 in cervical cancer cells. Serum starvation sequentially induced CREB1, then miR-320a, then reduced VDAC1 to facilitate mitophagy. Promoter cloning and deletion mapping, ChIP (CREB1 at miR-320a promoter), overexpression/knockdown experiments, immunoblot for VDAC1 and mitophagy markers Oncotarget Medium 26472185
2011 A TSH-CREB1-miRNA loop controls thyroid cell proliferation: thyrotropin (TSH) activates CREB1, which binds the regulatory regions of five specific miRNAs (miR-1, miR-28-A, miR-290-5p, miR-296-3p, miR-297a) and suppresses their expression; three of these miRNAs target CREB1, forming a feedback loop required for TSH-driven thyroid cell growth. ChIP (CREB1 binding to miRNA regulatory regions), overexpression of miRNAs, reporter assays, TSH stimulation of thyroid cells Molecular endocrinology Medium 21816899
2015 E2-induced PI3K/AKT pathway activation drives CREB1 phosphorylation and CREB1-mediated transcriptional activity that controls 17β-estradiol (E2)-induced cell proliferation. ERα residues L429 and A430 are required for E2-induced PI3K/AKT/CREB1 pathway activation; mutation of these residues abolishes E2-induced CREB1 phosphorylation and proliferation. Stable cell lines expressing L429A,A430G-ERα mutants, PI3K/AKT inhibition, CREB1 reporter assays, proliferation assays Cellular signalling Medium 26348925
2018 CDK5 (PKA/cAMP-independent) maintains CREB1 activation in glioma stem cells (GSCs) to support self-renewal. Pharmacological CDK5 inhibition suppresses CREB1 activation in vitro and in GSC xenograft tumors. A Drosophila genetic suppressor screen identified dCdk5 as a critical regulator, with human CDK5 (79% identity) validated as the ortholog. Drosophila genetic suppressor screen, CDK5 pharmacological inhibition, GSC self-renewal assays in vitro and xenograft tumors, TCGA data analysis Cell reports Medium 29742423
2018 SETD2-mediated H3K36 trimethylation (H3K36me3) is required for CREB1 phosphorylation and ERK pathway activation in NSCLC cells; a SETD2 missense mutation (p.T1171K) found in cisplatin-resistant metastatic NSCLC impairs H3K36me3 and CREB1 phosphorylation, conferring cisplatin resistance. Suppression of either SETD2 or CREB1 reduced cisplatin sensitivity. NGS identification of SETD2 mutation, ectopic expression of mutant SETD2, CREB1 siRNA knockdown, measurement of H3K36me3 and CREB1 phosphorylation, cisplatin cytotoxicity assays Oncogene Medium 30093630
2019 DJ-1 directly interacts with CaMKKβ and modulates CaMKIV/CREB1 (Ser133) phosphorylation to regulate tyrosine hydroxylase (TH) expression. In Dj-1 knockout mouse substantia nigra, CaMKIV phosphorylation, CREB1 Ser133 phosphorylation, and TH levels are all reduced. siRNA knockdown of Creb1 abolishes DJ-1's effect on TH. Co-immunoprecipitation (DJ-1 with CaMKKβ), Dj-1 knockout mice, siRNA knockdown of Creb1, immunoblot for phospho-CaMKIV and phospho-CREB1 Ser133 Journal of cellular physiology Medium 31232473
2021 CREB1 is constitutively active in prostate luminal (but not basal) cells and transcriptionally activates ING4 and its E3 ligase JFK. CREB1-dependent transient ING4 expression is required for luminal cell induction; failure to downregulate ING4 causes luminal cell death. Oncogenic PTEN loss causes constitutive CREB1 activation, which suppresses ING4, disrupting luminal differentiation. RNA-Seq, CREB1 blocking (pharmacological), overexpression/knockdown constructs, identification of ING4 and JFK as CREB1 transcriptional targets, PTEN-KO oncogenic transformation model, IHC of primary prostate tumors, xenograft tumor growth assay Oncogene Medium 33846571
2022 EBOV VP35 binds human AKIP1, which activates PKA and its downstream transcription factor CREB1. During Ebola infection, CREB1 is recruited into viral ribonucleoprotein complexes in viral inclusion bodies (VIBs) and is required for viral replication. AKIP1 depletion or PKA-CREB1 inhibition dramatically impairs EBOV replication. VP35-dependent CREB1 activation also upregulates coagulation genes THBD and SERPINB2. Co-immunoprecipitation (VP35-AKIP1), confocal colocalization in VIBs, siRNA depletion of AKIP1, PKA-CREB1 pharmacological inhibition, EBOV replication assays, transcriptomic analysis of CREB1 target genes Nature communications High 35474062
2023 Mettl3 (m6A methyltransferase) modulates the stability of Creb1 mRNA in an m6A-dependent manner in iNKT cells; Mettl3 deficiency decreases Creb1 mRNA stability and reduces Creb1 protein and phosphorylation levels. Conditional ablation of Creb1 in DP thymocytes phenocopies Mettl3 loss; ectopic Creb1 expression rescues developmental defects in Mettl3-deficient iNKT cells. Conditional KO of Mettl3 and Creb1 in DP thymocytes, transcriptomic and epi-transcriptomic analyses (m6A mapping), ectopic Creb1 expression rescue, flow cytometry, cytokine secretion assays Cell reports High 37267102
2023 Cullin-5 acts as an E3 ubiquitin ligase that ubiquitylates and degrades CREB1 protein, especially under proteotoxic stress. Cullin-5 deficiency leads to CREB1 accumulation and activation of CREB1-CCL2 signaling, promoting monocyte/MDSC accumulation and T-cell reduction in the tumor microenvironment. CRISPR-Cas9 genome-wide screen and Sleeping Beauty transposon mutagenesis in mice, ubiquitylation assay (Cullin-5 ubiquitylates CREB1), CREB1 inhibitor treatment, immune cell profiling by flow cytometry Science advances High 36662868
2021 CREB1 directly binds the promoter of CCAT1 lncRNA and activates its transcription to sustain MYC expression and cell proliferation. Additionally, in the absence of CREB1, competition between CREB1 and p65 for CBP/p300 is unbalanced, leading to NF-κB pathway activation and EMT in colorectal cancer cells. CREB1 CRISPR knockout in HCT116 cells, monitoring of 45 signaling pathways, ChIP (CREB1 at CCAT1 promoter), co-activator competition assay Science China. Life sciences Medium 35696016
2019 CREB1 acts as a transcription factor that binds the promoter of the Lin28 gene to activate Lin28 expression; CREB1 also directly binds the VASP promoter. Through this dual transcriptional control, CREB1 activates a CREB1/Lin28/miR-638/VASP interactive network promoting cell proliferation and migration in breast cancer. ChIP (CREB1 binding at Lin28 and VASP promoters), reporter assays, RNA-binding protein assays, overexpression/knockdown International journal of biological sciences Medium 31754343
2020 Norepinephrine (NE) induces CREB1 phosphorylation, and phosphorylated CREB1 binds to the miR-373 promoter to transcriptionally activate miR-373 expression, which promotes colon cancer cell proliferation and invasion through TIMP2 and APC suppression. ChIP (pCREB1 at miR-373 promoter), reporter assays, siRNA/overexpression of CREB1 and miR-373, in vitro and in vivo tumor models Molecular oncology Medium 32118353
2023 CREB1 transcriptionally activates SCD (stearoyl-CoA desaturase) via direct promoter binding; SCD increases monounsaturated fatty acid availability and thereby confers ferroptosis resistance. PKA inhibition reduces CREB1 activity and sensitizes NSCLC cells to ferroptosis inducers; SCD overexpression rescues the effect of CREB1 knockdown. High-throughput ChIP screening, dual-luciferase assay, CREB1 knockdown, SCD overexpression rescue, lipid peroxidation assays, xenograft tumor experiments Respiratory research Medium 37957645
2021 CREB1 directly binds to the promoter of HLA-E and activates its transcription in multiple myeloma cells. Pharmacological or genomic inhibition of CREB1 reduces HLA-E levels even in the presence of IFN-γ, thereby restoring NK cell-mediated cytotoxicity against MM cells. ChIP (CREB1 at HLA-E promoter), CREB1 knockdown/knockout and pharmacological inhibition, NK cell cytotoxicity assays, IFN-γ stimulation Leukemia Medium 38902472
2024 HTR2B (serotonin receptor) signaling activates S6K1 via Akt/mTOR, which phosphorylates CREB1 at Ser133, promoting CREB1 nuclear translocation. Nuclear phospho-CREB1 then binds the CREB1 half-site (GTCA) in the ZEB1 promoter to transcriptionally activate ZEB1, driving EMT and colorectal cancer metastasis. Pharmacological blocking and genetic knockdown of HTR2B, ChIP (pCREB1 at ZEB1 promoter), reporter assay with CREB1 half-site, phospho-CREB1 nuclear translocation assay, in vivo metastasis mouse models Molecular cancer research Medium 38381131
2021 CREB1 directly binds the promoter of SRGN to activate its transcription in nasopharyngeal carcinoma. CREB1 expression is controlled upstream by the FoxO1-miR-148a-5p axis (FoxO1 activates miR-148a-5p transcription; miR-148a-5p targets CREB1). STAT3 suppression upregulates FoxO1, leading to miR-148a-5p-mediated downregulation of CREB1 and SRGN. EMSA and ChIP (CREB1/FoxO1 binding at SRGN/miR-148a-5p promoters), dual-luciferase reporter assay, RIP assay, xenograft tumor model, siRNA knockdown Laboratory investigation Medium 35562411
2022 CREB1 binds to the promoter of the lncRNA PVT1 and activates its transcription in cardiac fibroblasts during TGF-β1-induced cardiac fibrosis, as confirmed by ChIP assay. ChIP assay (CREB1 at PVT1 promoter), luciferase reporter assay, siRNA knockdown, in vitro and in vivo cardiac fibrosis models International journal of cardiology Medium 35063587
2023 CREB1 and progesterone receptor (PGR) bind directly to the PTPN11 (SHP2) core promoter (-229 to +1 bp) in response to progesterone and cAMP during uterine stromal decidualization, as confirmed by EMSA and ChIP. Knockdown of either PGR or CREB1 significantly inhibits SHP2 expression induced by medroxyprogesterone acetate and cAMP. Luciferase reporter with promoter deletion mapping, EMSA, ChIP, siRNA knockdown of PGR and CREB1 in human endometrial stromal cells The FEBS journal Medium 37786383
2011 Striatal CREB1 in medium spiny neurons negatively regulates sensitivity to psychostimulants (cocaine, amphetamine). Postnatal deletion of CREB1 in these neurons increased psychostimulant sensitivity; loss of CREB1 was accompanied by rapid upregulation of the related transcription factor CREM, suggesting partial redundancy. Striatal deletion of CBP (CREB1 coactivator) produced even greater psychostimulant sensitivity. Cre/lox conditional KO of CREB1 or CBP in striatal medium spiny neurons, locomotor and sensitization behavioral assays, qRT-PCR and immunohistochemistry for CREM Psychopharmacology Medium 21766169
2019 In C. elegans, a specific isoform of CREB1/CRH-1 (CRH-1e) is primarily responsible for long-term memory (LTM) formation. Expression of CRH-1e in RIM neurons is sufficient to rescue LTM defects in crh-1 null mutants. Two amino acids, K247 and K266, within CREB1/CRH-1 are required for LTM-related functions but dispensable for innate chemotaxis behavior. Isoform-specific null mutants, neuron-specific rescue expression, site-directed mutagenesis (K247, K266), LTM behavioral assays, neuron silencing during training The Journal of neuroscience Medium 31413073
2024 Forskolin-driven neuronal reprogramming of human somatic cells operates via the cAMP-CREB1-JNK signaling axis: forskolin upregulates cAMP-CREB1 expression and downregulates JNK expression to convert somatic cells into induced neurons (FiNs). Small-molecule-driven reprogramming, western blot for cAMP/CREB1/JNK pathway components, immunofluorescence for neuronal markers, electrophysiological activity recordings in vitro and survival in vivo Theranostics Medium 38389831
2024 CREB1 signaling promotes ADT-induced neuroendocrine differentiation (NED) in prostate cancer cells by enhancing EZH2-mediated epigenetic repression of REST. Genetic rescue experiments showed that ADT induces NED through EZH2's repression of REST, with ADT-activated CREB1 signaling enhancing EZH2 activity. CREB1 signaling also directly represses REST expression. REST overexpression/knockdown, CREB1 signaling inhibition, EZH2 inhibition, genetic rescue experiments, ADT treatment in PCa cell lines and mouse xenografts, patient sample analysis Cell death discovery Medium 38777812
2021 CREB1 directly binds the promoter of miR-922 in liver cancer cells (confirmed by ChIP-PCR), activating its transcription. miR-922 then targets and suppresses ARID2 expression (confirmed by dual luciferase), enhancing malignant behavior. ChIP-PCR (CREB1 at miR-922 promoter), dual luciferase reporter assay, RIP assay, ARID2 overexpression rescue, xenograft tumor models Oncology reports Medium 33786634
2022 Regorafenib inhibits p38 kinase phosphorylation and downstream Creb1/Klf4 activity in macrophages, reversing M2 polarization toward M1. ChIP confirmed p38/Creb1/Klf4 activity at relevant promoters. This mechanism is independent of anti-angiogenic effects. ChIP (Creb1/Klf4 at target genes), p38 kinase inhibitor, MAPK14 knockdown, macrophage polarization markers (flow cytometry, ELISA, qRT-PCR), in vivo syngeneic liver cancer models Journal for immunotherapy of cancer Medium 33753566
2022 CRTC2 and CREB1 act as transcriptional activators of miR-93-3p in renal tubular epithelial cells exposed to calcium oxalate crystals; CREB1/CRTC2 binding to the miR-93-3p promoter was confirmed by EMSA and ChIP-qPCR. EMSA, ChIP-qPCR (CREB1/CRTC2 at miR-93-3p promoter), dual-luciferase reporter assay, siRNA knockdown, in vivo mouse model Journal of nanobiotechnology Medium 40069788
1990 The human CREB1 gene was assigned to chromosome 2q32.3-q34 using somatic cell hybrid Southern blot analysis and in situ hybridization. CREB1 was identified as a nuclear phosphoprotein involved in transcriptional regulation of cAMP-inducible genes. Southern blot analysis of mouse-human somatic cell hybrids, in situ hybridization, chromosome 2 translocation mapping Genomics High 2142119

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous histiocytoma. Genes, chromosomes & cancer 213 17724745
2012 Tumors with EWSR1-CREB1 and EWSR1-ATF1 fusions: the current status. The American journal of surgical pathology 195 22510762
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
2008 The Creb1 coactivator Crtc1 is required for energy balance and fertility. Nature medicine 168 18758446
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
2022 CircEZH2/miR-133b/IGF2BP2 aggravates colorectal cancer progression via enhancing the stability of m6A-modified CREB1 mRNA. Molecular cancer 136 35773744
2011 The CREB1-BDNF-NTRK2 pathway in depression: multiple gene-cognition-environment interactions. Biological psychiatry 131 21215389
2021 Regorafenib enhances antitumor immunity via inhibition of p38 kinase/Creb1/Klf4 axis in tumor-associated macrophages. Journal for immunotherapy of cancer 120 33753566
2016 Downregulation of microRNA-27b-3p enhances tamoxifen resistance in breast cancer by increasing NR5A2 and CREB1 expression. Cell death & disease 94 27809310
2014 Active CREB1 promotes a malignant TGFβ2 autocrine loop in glioblastoma. Cancer discovery 75 25084773
2022 Saffron essential oil ameliorates CUMS-induced depression-like behavior in mice via the MAPK-CREB1-BDNF signaling pathway. Journal of ethnopharmacology 69 36126781
2016 The microRNA miR-124 suppresses seizure activity and regulates CREB1 activity. Expert reviews in molecular medicine 68 26996991
2023 CREB1-driven CXCR4hi neutrophils promote skin inflammation in mouse models and human patients. Nature communications 65 37736772
2023 Chronic stress promotes colorectal cancer progression by enhancing glycolysis through β2-AR/CREB1 signal pathway. International journal of biological sciences 54 37151872
2018 UCA1 promotes cell proliferation and invasion of gastric cancer by targeting CREB1 sponging to miR-590-3p. Cancer medicine 53 29516678
2017 The cAMP responsive element-binding (CREB)-1 gene increases risk of major psychiatric disorders. Molecular psychiatry 48 29158582
2013 MicroRNA-200b targets CREB1 and suppresses cell growth in human malignant glioma. Molecular and cellular biochemistry 47 23543137
2017 Luteolin inhibits colorectal cancer cell epithelial-to-mesenchymal transition by suppressing CREB1 expression revealed by comparative proteomics study. Journal of proteomics 46 28391045
2013 MTOR inhibition attenuates DNA damage and apoptosis through autophagy-mediated suppression of CREB1. Autophagy 44 24189100
2018 Acquired SETD2 mutation and impaired CREB1 activation confer cisplatin resistance in metastatic non-small cell lung cancer. Oncogene 43 30093630
2016 MiR-582-5p/miR-590-5p targeted CREB1/CREB5-NF-κB signaling and caused opioid-induced immunosuppression in human monocytes. Translational psychiatry 41 26978739
2015 CREB1-driven expression of miR-320a promotes mitophagy by down-regulating VDAC1 expression during serum starvation in cervical cancer cells. Oncotarget 41 26472185
2019 CREB1 induced lncRNA HAS2-AS1 promotes epithelial ovarian cancer proliferation and invasion via the miR-466/RUNX2 axis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 40 31082772
2016 Understanding the CREB1-miRNA feedback loop in human malignancies. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 40 27059735
2022 CREB1 contributes colorectal cancer cell plasticity by regulating lncRNA CCAT1 and NF-κB pathways. Science China. Life sciences 39 35696016
2010 CCDC6 represses CREB1 activity by recruiting histone deacetylase 1 and protein phosphatase 1. Oncogene 38 20498639
2020 Intracranial myxoid mesenchymal tumor with EWSR1-CREB1 gene fusion: a case report and literature review. Brain tumor pathology 37 32215804
2018 A CREB1/miR-433 reciprocal feedback loop modulates proliferation and metastasis in colorectal cancer. Aging 37 30523220
2007 Clinical and genetic dissection of anger expression and CREB1 polymorphisms in major depressive disorder. Biological psychiatry 37 17300755
2019 The HBx-CTTN interaction promotes cell proliferation and migration of hepatocellular carcinoma via CREB1. Cell death & disease 36 31138777
2018 CDK5 Inhibition Resolves PKA/cAMP-Independent Activation of CREB1 Signaling in Glioma Stem Cells. Cell reports 35 29742423
2018 Knockdown of CREB1 promotes apoptosis and decreases estradiol synthesis in mouse granulosa cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 34 30021350
1990 Assignment of the human gene for CREB1 to chromosome 2q32.3-q34. Genomics 34 2142119
2016 Integrative analysis identifies targetable CREB1/FoxA1 transcriptional co-regulation as a predictor of prostate cancer recurrence. Nucleic acids research 32 26743006
2020 Norepinephrine-CREB1-miR-373 axis promotes progression of colon cancer. Molecular oncology 31 32118353
2019 GATA6 suppresses migration and metastasis by regulating the miR-520b/CREB1 axis in gastric cancer. Cell death & disease 31 30674866
2011 A TSH-CREB1-microRNA loop is required for thyroid cell growth. Molecular endocrinology (Baltimore, Md.) 31 21816899
2020 Overexpression of XIST facilitates cell proliferation, invasion and suppresses cell apoptosis by reducing radio-sensitivity of glioma cells via miR-329-3p/CREB1 axis. European review for medical and pharmacological sciences 30 32271437
2018 Clear Cell Odontogenic Carcinoma: Occurrence of EWSR1-CREB1 as Alternative Fusion Gene to EWSR1-ATF1. Head and neck pathology 30 30047065
2021 Hepatitis B Virus DNA Polymerase Restrains Viral Replication Through the CREB1/HOXA Distal Transcript Antisense RNA Homeobox A13 Axis. Hepatology (Baltimore, Md.) 28 32314410
2020 Circular RNA hsa_circ_0075828 promotes bladder cancer cell proliferation through activation of CREB1. BMB reports 27 31072448
2021 lncRNA MALAT1 Regulates Mouse Granulosa Cell Apoptosis and 17β-Estradiol Synthesis via Regulating miR-205/CREB1 Axis. BioMed research international 25 33681369
2018 CREB1, a direct target of miR-122, promotes cell proliferation and invasion in bladder cancer. Oncology letters 25 30127997
2023 Inhibition of PKA/CREB1 pathway confers sensitivity to ferroptosis in non-small cell lung cancer. Respiratory research 24 37957645
2019 CREB1/Lin28/miR-638/VASP Interactive Network Drives the Development of Breast Cancer. International journal of biological sciences 24 31754343
2024 Serotonin Receptor HTR2B Facilitates Colorectal Cancer Metastasis via CREB1-ZEB1 Axis-Mediated Epithelial-Mesenchymal Transition. Molecular cancer research : MCR 23 38381131
2016 Aripiprazole Increases the PKA Signalling and Expression of the GABAA Receptor and CREB1 in the Nucleus Accumbens of Rats. Journal of molecular neuroscience : MN 23 26894264
2007 Lyl1 interacts with CREB1 and alters expression of CREB1 target genes. Biochimica et biophysica acta 23 18160048
2020 Combining Bioinformatics and Experiments to Identify CREB1 as a Key Regulator in Senescent Granulosa Cells. Diagnostics (Basel, Switzerland) 22 32403258
2017 GNB3 and CREB1 gene polymorphisms combined with negative life events increase susceptibility to major depression in a Chinese Han population. PloS one 22 28225778
2010 Epistatic interaction of CREB1 and KCNJ6 on rumination and negative emotionality. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 22 20943350
2020 Primary pulmonary myxoid sarcoma with EWSR1-CREB1 fusion: a case report and review of the literature. Diagnostic pathology 21 32039736
2018 Effects of CREB1 gene silencing on cognitive dysfunction by mediating PKA-CREB signaling pathway in mice with vascular dementia. Molecular medicine (Cambridge, Mass.) 21 30134805
2015 Estrogen receptor α L429 and A430 regulate 17β-estradiol-induced cell proliferation via CREB1. Cellular signalling 20 26348925
2022 CREB1 promotes proliferation and differentiation by mediating the transcription of CCNA2 and MYOG in bovine myoblasts. International journal of biological macromolecules 19 35777504
2017 CREB1 and Smad3 mediate TGF‑β3‑induced Smad7 expression in rat hepatic stellate cells. Molecular medicine reports 18 28983617
2022 CREB1 transcription-activated lncRNA PVT1 promotes cardiac fibrosis via miR-145/HCN1 axis. International journal of cardiology 17 35063587
2020 Silencing SGK1 alleviates osteoarthritis through epigenetic regulation of CREB1 and ABCA1 expression. Life sciences 17 33171176
2015 MicroRNA-506 inhibits esophageal cancer cell proliferation via targeting CREB1. International journal of clinical and experimental pathology 17 26617801
2024 Forskolin-driven conversion of human somatic cells into induced neurons through regulation of the cAMP-CREB1-JNK signaling. Theranostics 16 38389831
2024 CREB1 promotes expression of immune checkpoint HLA-E leading to immune escape in multiple myeloma. Leukemia 16 38902472
2022 Ebola virus VP35 hijacks the PKA-CREB1 pathway for replication and pathogenesis by AKIP1 association. Nature communications 16 35474062
2022 miR-125b-5p upregulation by TRIM28 induces cisplatin resistance in non-small cell lung cancer through CREB1 inhibition. BMC pulmonary medicine 16 36476351
2021 Aberrant CREB1 activation in prostate cancer disrupts normal prostate luminal cell differentiation. Oncogene 16 33846571
2020 EZH2 inhibition promotes ANGPTL4/CREB1 to suppress the progression of ulcerative colitis. Life sciences 16 32194081
2020 CREB1-induced miR-1204 promoted malignant phenotype of glioblastoma through targeting NR3C2. Cancer cell international 16 32280303
2019 miR-133a-3p promotes apoptosis and induces cell cycle arrest by targeting CREB1 in retinoblastoma. Archives of medical science : AMS 16 32542098
2021 Long coding RNA CCAT2 enhances the proliferation and epithelial-mesenchymal transition of cervical carcinoma cells via the microRNA-493-5p/CREB1 axis. Bioengineered 15 34499007
2011 CREB1 and CREB-binding protein in striatal medium spiny neurons regulate behavioural responses to psychostimulants. Psychopharmacology 15 21766169
2023 Cullin-5 deficiency orchestrates the tumor microenvironment to promote mammary tumor development through CREB1-CCL2 signaling. Science advances 14 36662868
2023 Progesterone and cAMP synergistically induce SHP2 expression via PGR and CREB1 during uterine stromal decidualization. The FEBS journal 14 37786383
2021 CREB1 acts via the miR‑922/ARID2 axis to enhance malignant behavior of liver cancer cells. Oncology reports 14 33786634
2020 miR-134-5p inhibition reduces infarct-induced cardiomyocyte apoptosis via Creb1 upregulation. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 14 32689640
2013 Creb1-Mecp2-(m)CpG complex transactivates postnatal murine neuronal glucose transporter isoform 3 expression. Endocrinology 14 23493374
2009 CREB1/ATF1 activation in photoreceptor degeneration and protection. Investigative ophthalmology & visual science 14 19643965
2024 The CREB1 inhibitor 666-15 maintains cartilage homeostasis and mitigates osteoarthritis progression. Bone & joint research 13 38163445
2024 Cardiopulmonary progenitors facilitate cardiac repair via exosomal transfer of miR-27b-3p targeting the SIK1-CREB1 axis. Cell proliferation 13 38185757
2024 Baicalein upregulates macrophage TREM2 expression via TrKB-CREB1 pathway to attenuate acute inflammatory injury in acute-on-chronic liver failure. International immunopharmacology 13 39047449
2023 Mettl3-m6A-Creb1 forms an intrinsic regulatory axis in maintaining iNKT cell pool and functional differentiation. Cell reports 13 37267102
2022 Magnesium promotes osteogenesis via increasing OPN expression and activating CaM/CaMKIV/CREB1 pathway. Journal of biomedical materials research. Part B, Applied biomaterials 13 35106922
2022 STAT3 regulates SRGN and promotes metastasis of nasopharyngeal carcinoma through the FoxO1-miR-148a-5p-CREB1 axis. Laboratory investigation; a journal of technical methods and pathology 13 35562411
2021 Long noncoding RNA XIST modulates microRNA-135/CREB1 axis to influence osteogenic differentiation of osteoblast-like cells in mice with tibial fracture healing. Human cell 13 34635983
2020 cAMP Response Element Binding Protein 1 (CREB1) Promotes Monounsaturated Fatty Acid Synthesis and Triacylglycerol Accumulation in Goat Mammary Epithelial Cells. Animals : an open access journal from MDPI 13 33066354
2019 MiR-155-5p affects Wilms' tumor cell proliferation and apoptosis via targeting CREB1. European review for medical and pharmacological sciences 13 30779069
2018 MicroRNA-205 affects mouse granulosa cell apoptosis and estradiol synthesis by targeting CREB1. Journal of cellular biochemistry 13 30556190
2022 MiR-654-3p Constrains Proliferation, Invasion, and Migration of Sinonasal Squamous Cell Carcinoma via CREB1/PSEN1 Regulatory Axis. Frontiers in genetics 12 35096015
2020 TGF‑β1 induces CREB1‑mediated miR‑1290 upregulation to antagonize lung fibrosis via Napsin A. International journal of molecular medicine 12 32319530
2019 DJ-1 regulates tyrosine hydroxylase expression through CaMKKβ/CaMKIV/CREB1 pathway in vitro and in vivo. Journal of cellular physiology 12 31232473
2019 Differential Regulation of Innate and Learned Behavior by Creb1/Crh-1 in Caenorhabditis elegans. The Journal of neuroscience : the official journal of the Society for Neuroscience 12 31413073
2024 Androgen deprivation induces neuroendocrine phenotypes in prostate cancer cells through CREB1/EZH2-mediated downregulation of REST. Cell death discovery 11 38777812
2023 The SIK1/CRTC2/CREB1 and TWIST1/PI3K/Akt/GSK3β signaling pathways mediated by microRNA-25-3p are altered in the schizophrenic rat brain. Frontiers in cellular neuroscience 11 36744005
2023 Geniposide improves depression by promoting the expression of synapse-related proteins through the Creb1/Six3os1 axis. Gene 11 37311497
2023 PIN1P1 is activated by CREB1 and promotes gastric cancer progression via interacting with YBX1 and upregulating PIN1. Journal of cellular and molecular medicine 11 37929660
2023 LncRNA TDRKH-AS1 promotes breast cancer progression via the miR-134-5p/CREB1 axis. Journal of translational medicine 11 38008726
2021 An insertion/deletion within the CREB1 gene identified using the RNA-sequencing is associated with sheep body morphometric traits. Gene 11 33484760
2020 CREB1 and BDNF gene polymorphisms are associated with early treatment response to escitalopram in panic disorder. Journal of affective disorders 11 33017682
2025 CREB1/CRTC2 regulated tubular epithelial-derived exosomal miR-93-3p promotes kidney injury induced by calcium oxalate via activating M1 polarization and macrophage extracellular trap formation. Journal of nanobiotechnology 10 40069788
2022 CREB1 Transcriptionally Activates LTBR to Promote the NF-κB Pathway and Apoptosis in Lung Epithelial Cells. Computational and mathematical methods in medicine 10 36118831
2022 Dysfunctional microRNA-144-3p/ZBTB20/ERK/CREB1 signalling pathway is associated with MK-801-induced schizophrenia-like abnormalities. Brain research 10 36335997
2021 Polymorphisms of COMT and CREB1 are associated with treatment-resistant depression in a Chinese Han population. Journal of neural transmission (Vienna, Austria : 1996) 10 34767111

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