Affinage

ZNF148

Zinc finger protein 148 · UniProt Q9UQR1

Length
794 aa
Mass
89.0 kDa
Annotated
2026-06-11
85 papers in source corpus 37 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ZNF148 (ZBP-89/BFCOL1) is a Krüppel-type C2H2 zinc finger transcription factor that binds GC-rich DNA elements to repress or activate target genes and thereby governs cell proliferation, differentiation, and tissue homeostasis (PMID:8943318, PMID:10899165). At its founding it was defined as a repressor of the gastrin promoter that competes with Sp1 at a shared GC-rich element (PMID:8943318), and it similarly represses the ODC and vimentin promoters by competing with or directly heterodimerizing with Sp1 (PMID:9685330, PMID:10777586, PMID:12771217). Its transcriptional output is determined by the co-regulators it recruits: it binds the histone acetyltransferases p300 and Gcn5/Trrap (PMID:10899165, PMID:21828133) and the deacetylase HDAC3 (PMID:19583777), using these to acetylate erythroid and globin loci (PMID:21828133) or to epigenetically silence p16(INK4a) (PMID:19583777). ZNF148 is a central node in p53/ARF-dependent growth control, directly stabilizing and nuclear-retaining p53 through a zinc-finger/p53-DNA-binding-domain interaction (PMID:11416144) and repressing the ARF promoter (PMID:32843651); its loss arrests proliferation in a p53-dependent manner in macrophages and fibroblasts (PMID:25212213, PMID:32843651). It also induces p21(waf1) by recruiting ATM to the promoter, and ATM reciprocally phosphorylates ZNF148 at Ser202 to potentiate this induction (PMID:16952553, PMID:17560543). Activity is further tuned by SUMOylation, which restrains synergy with Sp1 and other activators (PMID:17940278). Through these mechanisms ZNF148 directs hematopoietic lineage choice and erythropoiesis as part of GATA-1/FOG-1 complexes and in redundancy with its paralog Zfp281 (PMID:18250154, PMID:24549639, PMID:31455666), drives a β-catenin feedforward loop in colorectal tumorigenesis (PMID:27758879), regulates TERT transcription and telomerase activity (PMID:28447668, PMID:37918959), and restrains insulin secretion, T-cell differentiation, and CD8+ effector/exhaustion programs (PMID:35603790, PMID:37288664, PMID:37948511, PMID:41896465). Across these contexts it functions context-dependently as both tumor suppressor and tumor promoter (PMID:36207293, PMID:40623191).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 1996 High

    Established ZNF148/ZBP-89 as a sequence-specific GC-rich DNA-binding repressor, defining the protein's core molecular activity by showing it competes with Sp1 at the gastrin promoter.

    Evidence Expression library screen, EMSA, and reporter assays at the gastrin EGF response element

    PMID:8943318

    Open questions at the time
    • Co-regulators mediating repression not yet identified
    • In vivo relevance untested
  2. 1998 High

    Generalized the Sp1-antagonism model to a second GC-box target, showing ZBP-89 inhibits Sp1-mediated ODC promoter activation, linking DNA binding to growth-related gene control.

    Evidence Yeast one-hybrid, co-purification, antibody supershift, and reporter assays in Drosophila SL2 cells

    PMID:9685330

    Open questions at the time
    • Whether repression is competitive or co-regulator-dependent unresolved at this stage
  3. 1997 Medium

    Connected ZBP-89 transcriptional activity to a cellular phenotype by showing overexpression blocks S-phase entry, at least partly via ODC repression.

    Evidence Thymidine/BrdU incorporation, flow cytometry, and ODC reporter assays in GH4/AGS cells

    PMID:9268691

    Open questions at the time
    • Single lab, single study
    • Mechanism linking ODC repression to arrest not fully dissected
  4. 2000 High

    Resolved how ZBP-89 controls target output by showing it directly binds p300 via its N-terminus and physically partners Sp1, providing the co-activator/co-repressor logic behind p21(waf1) and vimentin regulation.

    Evidence Co-IP, DNase I footprinting, deletion mutagenesis, and reporter assays (p21 and vimentin promoters)

    PMID:10777586 PMID:10899165 PMID:12771217

    Open questions at the time
    • Whether p300 and HDAC recruitment are mutually exclusive unclear
    • Context determinants of activation vs repression not defined
  5. 2001 High

    Defined a co-factor mechanism for tumor suppression by demonstrating ZBP-89 directly binds, stabilizes, and nuclear-retains p53, enhancing p53 activity and driving growth arrest/apoptosis.

    Evidence Co-IP, domain mapping, heterokaryon nuclear export assay, and flow cytometry in GI cell lines

    PMID:11416144

    Open questions at the time
    • Mechanism of p53 stabilization independent of MDM2 not fully resolved
    • In vivo significance addressed only later
  6. 2004 High

    Showed ZBP-89 can also trigger apoptosis independently of p53 via JNK activation and MKP6/Bcl-xL/Mcl-1 repression, establishing a parallel death pathway.

    Evidence Dominant-negative JNK, kinase inhibitors, siRNA, and microarray with PARP cleavage readouts

    PMID:14963412

    Open questions at the time
    • Direct vs indirect repression of MKP6 not distinguished
    • Single lab
  7. 2007 High

    Established a reciprocal ATM–ZBP-89 signaling module: ZBP-89 recruits ATM to the p21 promoter and ATM phosphorylates ZBP-89 at Ser202 to potentiate p21 induction.

    Evidence Co-IP, ChIP, immunodepletion, in vitro kinase assay, and S202A mutagenesis

    PMID:16952553 PMID:17560543

    Open questions at the time
    • Structural basis of ATM recruitment unknown
    • Generality beyond HDACi context untested
  8. 2007 High

    Identified SUMOylation at synergy-control motifs as a post-translational switch restraining ZBP-89 cooperation with Sp1 and other activators without altering simple site competition.

    Evidence SUMOylation assays, acceptor-site mutagenesis, and reporter assays

    PMID:17940278

    Open questions at the time
    • SUMO ligase/protease controlling this not identified
    • Physiological triggers of SUMOylation unknown
  9. 2009 High

    Demonstrated an epigenetic silencing mechanism whereby ZBP-89 recruits HDAC3 to deacetylate the p16(INK4a) promoter, with loss driving senescence reversible by p16 silencing.

    Evidence siRNA, ChIP, Co-IP, immunofluorescence, and beta-galactosidase senescence assays

    PMID:19583777

    Open questions at the time
    • Selectivity for HDAC3 over other HDACs mechanism unclear
    • Single lab
  10. 2008 High

    Placed ZBP-89 in hematopoietic transcriptional complexes by showing it associates with GATA-1/FOG-1, co-occupies erythroid/megakaryocyte loci, and is genetically required for definitive erythropoiesis and megakaryopoiesis in vivo.

    Evidence GATA-1 interactome proteomics, ChIP, zebrafish morpholino, and mouse knockout

    PMID:18250154

    Open questions at the time
    • Direct vs bridged GATA-1 interaction not defined
    • Target genes mediating phenotype incompletely mapped
  11. 2011 High

    Linked ZBP-89 to acetyltransferase recruitment in erythroid cells by showing it binds p300 and Gcn5/Trrap and is required for Gcn5 occupancy and globin gene H3 acetylation.

    Evidence Co-IP, ChIP co-occupancy, shRNA, and HDAC-inhibitor rescue in erythroid cells

    PMID:21828133

    Open questions at the time
    • How ZBP-89 toggles between HAT and HDAC partners not resolved
  12. 2014 High

    Defined ZBP-89 as a hematopoietic lineage regulator that represses PU.1 while activating SCL/Tal1 and GATA-1, with deletion causing a myeloid-to-B lymphoid switch.

    Evidence Conditional knockout, bone marrow transplantation, ChIP, and luciferase reporters

    PMID:24549639

    Open questions at the time
    • Direct vs indirect contributions to each target not fully separated
  13. 2014 High

    Provided in vivo genetic proof that ZBP-89 restrains the p53 pathway by showing Zfp148 deficiency reduces atherosclerosis in a strictly p53-dependent, macrophage-intrinsic manner.

    Evidence Gene-trap mouse, bone marrow transplantation, Trp53 epistasis, and phospho-p53/BrdU readouts

    PMID:25212213

    Open questions at the time
    • Molecular link from ZBP-89 loss to p53 activation defined only later via ARF
  14. 2020 Medium

    Mechanistically connected ZBP-89 to p53 activation by identifying direct ARF promoter binding/repression, with loss driving ARF- and p53-dependent cell-cycle arrest.

    Evidence ChIP-seq, MEF proliferation assays, and p53/ARF genetic epistasis

    PMID:32843651

    Open questions at the time
    • No genetic ZNF148–TP53 interaction observed in human cancer cells (negative result)
    • Indirect contributions to ARF activation not fully resolved
  15. 2016 High

    Identified a β-catenin feedforward loop in colorectal cancer in which ZBP-89 activates CTNNB1 and is itself induced by β-catenin/TCF, with deletion reducing polyps.

    Evidence ChIP, EMSA, siRNA, reporter assays, and conditional KO in APC-deleted mice

    PMID:27758879

    Open questions at the time
    • Co-regulators converting ZBP-89 into a CTNNB1 activator unknown
  16. 2017 High

    Established allele-specific regulation of telomerase by showing ZNF148 binds the rs36115365-C CLPTM1L/TERT locus and is required for TERT expression, telomerase activity, and telomere length.

    Evidence Allele-specific proteomic pulldown, recombinant protein binding, siRNA, and telomerase/telomere assays

    PMID:28447668

    Open questions at the time
    • Whether effect is activating or repressive at this locus clarified by later TERT promoter work
  17. 2023 Medium

    Showed ZNF148 directly activates the wild-type TERT promoter at position -124 and binds the mutant allele poorly, defining it as an activating telomerase regulator.

    Evidence Allele-specific proteomic pulldown, reporter assays, and telomerase activity assays

    PMID:37918959

    Open questions at the time
    • Co-activators at the TERT promoter not identified
    • Single lab
  18. 2019 High

    Expanded ZNF148's regulatory repertoire across tissues, demonstrating paralog redundancy with Zfp281 in erythropoiesis, NICD1-competitive repression of Notch in liver cancer stem cells, and activation of autophagy genes in smooth muscle.

    Evidence Double conditional KO with Co-IP/ChIP; competitive binding and xenografts; siRNA/ChIP in smooth muscle

    PMID:31025534 PMID:31455666 PMID:31874246

    Open questions at the time
    • Degree of functional overlap with Zfp281 across other tissues unmapped
  19. 2022 High

    Defined opposing oncogenic and tumor-suppressive roles by showing ZNF148 is MYC-repressed and itself represses stemness drivers ID1/ID3 in breast cancer.

    Evidence shRNA, CRISPR/Cas9, RNA-seq, and ChIP-seq identifying direct ID1/ID3 targets

    PMID:36207293

    Open questions at the time
    • Determinants of tumor-suppressor vs promoter behavior across cancers unclear
  20. 2022 High

    Revealed a metabolic role in β cells, where Zfp148 deletion enhances amino-acid-induced Ca2+ influx and insulin secretion by remodeling amino acid/intermediary metabolism gene expression.

    Evidence β-cell-specific conditional KO with Ca2+ imaging, RNA-seq, and proteomics

    PMID:35603790

    Open questions at the time
    • Direct vs indirect transcriptional control of metabolic enzymes not fully dissected
  21. 2023 High

    Identified an exocytosis-regulatory mechanism whereby ZNF148 represses S100A16 to control annexin A2 trafficking and insulin vesicle exocytosis.

    Evidence siRNA in human islets, CRISPR KO in SC-β cells, transcriptomics, and subcellular fractionation

    PMID:37288664

    Open questions at the time
    • Whether S100A16 repression is direct not fully established
  22. 2023 High

    Established T-lineage roles by showing Zfp148 (with Zfp281) drives intrathymic CD4+ differentiation and TH2 cytokine chromatin opening.

    Evidence Conditional KO, single-cell RNA-seq, spatial transcriptomics, ATAC-seq, and Co-IP

    PMID:37948511

    Open questions at the time
    • Zfp148's own protein partners in T cells less defined than the paralog's Gata3 interaction
  23. 2020 Medium

    Showed ZNF148 phosphorylation by ERK at Ser306 reprograms it into a FOXM1 partner that promotes Snail transcription and invasion in SDHB-deficient GIST.

    Evidence Phosphorylation assays, Co-IP, ChIP, reporter, and invasion assays

    PMID:32060966

    Open questions at the time
    • Single lab
    • Generality of ERK-driven ZNF148/FOXM1 axis beyond GIST untested
  24. 2025 High

    Demonstrated a cancer-specific enhancer mechanism in which ZNF148 physically binds p63 and co-occupies a CCND1 eRNA to drive cyclin D1 and proliferation.

    Evidence Proteomics, Co-IP, ChIP-seq, and eRNA reporter assays in HNSCC

    PMID:40623191

    Open questions at the time
    • Why the axis is silent in normal epithelium not mechanistically resolved
  25. 2026 High

    Defined ZFP148 as a brake on cytolytic CD8+ T-cell effector differentiation by limiting effector-TF chromatin accessibility and directly repressing KLF2, with ablation synergizing with PD-1 blockade.

    Evidence Conditional KO, chronic infection and tumor models, ATAC-seq, ChIP-seq/CUT&RUN, and immunotherapy combination

    PMID:41896465

    Open questions at the time
    • Upstream signals controlling ZFP148 in T cells unknown
    • Full effector-program target set beyond KLF2 incomplete

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved what molecular switch dictates whether ZNF148 acts as activator or repressor and tumor suppressor or promoter at a given locus, including how post-translational modifications and partner availability select between HAT and HDAC recruitment.
  • No unifying structural or biochemical model of activation vs repression
  • Genome-wide rules linking modification state to co-regulator choice undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 6 GO:0140110 transcription regulator activity 6 GO:0098772 molecular function regulator activity 3
Localization
GO:0005654 nucleoplasm 4 GO:0005634 nucleus 2
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-4839726 Chromatin organization 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1643685 Disease 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-168256 Immune System 2
Partners
ATMEP300FOXM1GATA1HDAC3SP1TP53TP63
Complex memberships
GATA-1/FOG-1 complexZBP-89–HDAC3 complexZBP-89–p300/Gcn5–Trrap complex

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 ZBP-89 (ZNF148) is a Krüppel-type C2H2 zinc finger transcription factor that binds specifically to the GC-rich gastrin EGF response element (GGGGCGGGGTGGGGGG) and inhibits both basal and EGF-induced gastrin promoter activity, functioning as a transcriptional repressor that competes with Sp1 at the same DNA element. Expression library screening, EMSA, reporter gene assays, in vitro binding assays Molecular and cellular biology High 8943318
1998 ZBP-89 binds to the GC box in the ornithine decarboxylase (ODC) promoter and inhibits Sp1-mediated activation of the ODC promoter. ZBP-89 was identified as the protein responsible for NF-ODC1 binding activity: ZBP-89 co-purified with NF-ODC1 activity, anti-ZBP-89 antibodies abolished NF-ODC1 binding, and the binding affinities of ZBP-89 and NF-ODC1 for 12 oligonucleotides were indistinguishable. Yeast one-hybrid screening, co-purification, antibody supershift, competitive binding assays, reporter gene assays in Drosophila SL2 cells The Journal of biological chemistry High 9685330
1997 ZBP-89 overexpression inhibits cell proliferation: DNA synthesis is inhibited and progression to S phase is blocked in immortalized GH4 and malignant AGS cell lines, at least in part through repression of ornithine decarboxylase promoter activity. 3H-thymidine incorporation, BrdU labeling, flow cytometry, reporter gene assay (ODC promoter) Biochemical and biophysical research communications Medium 9268691
2000 ZBP-89 binds to the human vimentin gene silencer element and heterodimerizes with Sp1 at this element. Co-immunoprecipitation and DNA affinity chromatography showed that Sp1 and ZBP-89 form a complex when bound to the silencer element. In vivo DMS footprinting (ligation-mediated PCR), EMSA, UV cross-linking, Southwestern blot, co-immunoprecipitation, DNA affinity chromatography The Journal of biological chemistry High 10777586
2000 ZBP-89 directly binds p300 (histone acetyltransferase co-activator) via its N-terminal domain, but does not directly bind Sp1. ZBP-89 co-precipitates with Sp1, and deletion of the ZBP-89 N-terminal domain abolishes both the p300 interaction and butyrate-mediated potentiation of p21(waf1) transcription. ZBP-89 binds to a specific element at -245 to -215 in the p21(waf1) promoter. Adenoviral overexpression, co-immunoprecipitation, DNase I footprinting, EMSA, deletion mutagenesis, reporter gene assays The Journal of biological chemistry High 10899165
2000 PTRF (polymerase I and transcript-release factor) interacts with the N-terminal zinc-finger domain of BFCOL1/ZBP-89 (identified by yeast two-hybrid), and recombinant PTRF enhances BFCOL1 binding to the mouse proalpha2(I) collagen proximal promoter in vitro. PTRF has a suppressive effect on collagen promoter activity in transfection assays. Yeast two-hybrid, recombinant protein binding assay, transient transfection reporter assay The Biochemical journal Medium 10727401
2001 ZBP-89 stabilizes p53 protein and enhances p53 transcriptional activity through direct protein-protein interaction. The DNA binding and C-terminal domains of p53 and the zinc finger domain of ZBP-89 mediate the interaction. ZBP-89 retains p53 in the nucleus (shown by heterokaryon assay) without preventing MDM2-p53 interaction. The p53 R273H mutation greatly reduced ZBP-89-mediated stabilization. Elevated ZBP-89 induces growth arrest and apoptosis in human gastrointestinal cell lines. Co-immunoprecipitation, domain deletion/point-mutation analysis, heterokaryon nuclear export assay, reporter gene assay, flow cytometry Molecular and cellular biology High 11416144
2003 ZBP-89 represses vimentin gene transcription by interacting with the transcriptional activator Sp1 via its N-terminal domain. The glutamine-rich region of Sp1 is required for vimentin activation, while ZBP-89 N-terminus mediates interaction with Sp1 and represses expression. Overexpression of hTAF(II)130 alleviates ZBP-89 repression. Transient transfection reporter assay, deletion constructs, overexpression in Schneider (S2) cells Nucleic acids research Medium 12771217
2003 ZBP-89 is required for constitutive STAT1 expression. A G-rich element (+171 to +179) in the first intron of STAT1 is critical for STAT1 promoter activity. ZBP-89 binds this element along with Sp1 and Sp3. siRNA-mediated reduction of ZBP-89 attenuated both basal and IFNγ-induced STAT1 expression and diminished caspase-3 and PARP activation. Site-directed mutagenesis, EMSA, siRNA knockdown, immunoblotting, reporter assay Nucleic acids research Medium 14654702
2004 ZBP-89 induces apoptosis through a p53-independent mechanism requiring JNK activation. ZBP-89 activates JNK via repression of JNK dephosphorylation by downregulating the dual-specificity phosphatase MKP6. ZBP-89-induced apoptosis proceeds through the mitochondrial pathway; JNK inhibition (by peptide inhibitor or dominant-negative JNK2) abrogates apoptosis, while ERK inhibition enhances it. ZBP-89 represses Bcl-xL and Mcl-1 expression. Ectopic expression, dominant-negative constructs, kinase inhibitors, protein dephosphorylation assays, oligonucleotide microarray, siRNA silencing, PARP cleavage assays Cell death and differentiation High 14963412
2006 ZBP-89 interacts with ATM in a butyrate/HDACi-dependent manner and recruits ATM to GC-rich elements of the p21(waf1) promoter. Co-immunoprecipitation revealed ATM associates with both the N-terminal and DNA binding domains of ZBP-89. Immunodepletion of ZBP-89 prevented recruitment of ATM to the p21(waf1) promoter in vitro. Silencing ZBP-89 blocked HDACi-induced phosphorylation of ATM(Ser1981) and p53(Ser15). Co-immunoprecipitation, mass spectrometry, chromatin immunoprecipitation (ChIP), DNA affinity precipitation, siRNA, serial deletion mapping Gastroenterology High 16952553
2007 ATM phosphorylates ZBP-89 at Ser202 (within an SQ motif in the zinc finger domain) both in vitro and in vivo. Disruption of the ATM phosphorylation motif (S202A) attenuated ZBP-89's ability to enhance p21(waf1) activation by butyrate and abrogated potentiation of butyrate-induced endogenous p21(waf1) expression. In vitro kinase assay, site-directed mutagenesis (S202A), reporter gene assay, immunoblotting Biochemical and biophysical research communications High 17560543
2007 ZBP-89 is post-translationally modified by SUMO at two conserved synergy control motifs flanking the DNA binding domain. Sumoylation inhibits functional cooperation (synergy) between ZBP-89 and Sp1 at promoters bearing multiple response elements, and inhibits ZBP-89 synergy with heterologous activators such as glucocorticoid receptor, through a conserved functional surface. Sumoylation does not directly alter ZBP-89's ability to compete with Sp-like factors from individual sites. Sumoylation assay, mutagenesis of SUMO acceptor sites, reporter gene assays, promoter analysis The Journal of biological chemistry High 17940278
2008 ZBP-89 is a component of multiprotein complexes involving GATA-1 and its cofactor FOG-1 in erythroid and megakaryocyte cells (identified by proteomics). ZBP-89 and GATA-1 co-occupy cis-regulatory elements of certain erythroid and megakaryocyte-specific genes by chromatin immunoprecipitation. Loss of ZBP-89 function in zebrafish and mice demonstrates an in vivo requirement for ZBP-89 in megakaryopoiesis and definitive erythropoiesis but not primitive erythropoiesis. Proteomics (GATA-1 interactome), chromatin immunoprecipitation, morpholino knockdown in zebrafish, mouse genetic knockout Molecular and cellular biology High 18250154
2009 ZBP-89 suppresses p16(INK4a) expression through an epigenetic mechanism: ZBP-89 recruits HDAC3 (not HDAC4) to the p16(INK4a) promoter, resulting in histone deacetylation. Knockdown of ZBP-89 stimulates cellular senescence reversible by p16 silencing. ZBP-89 and HDAC3 form a complex (shown by co-immunoprecipitation and immunofluorescence co-localization). siRNA knockdown, chromatin immunoprecipitation, co-immunoprecipitation, immunofluorescence, beta-galactosidase senescence assay, reporter gene assay The FEBS journal High 19583777
2009 ZBP-89 plays a positive role in C2C12 myogenesis: overexpression promotes down-regulation of Pax7 and up-regulation of MRF4 and MyoD, p21, and Rb, while down-regulating cyclinA and cyclinD1. ZBP-89 levels increase during myogenesis, and siRNA-mediated ZBP-89 knockdown delays the myogenic program. ChIP assays confirmed ZBP-89 occupancy at target gene loci. Adenoviral overexpression, siRNA knockdown, qRT-PCR, chromatin immunoprecipitation, flow cytometry Biochimica et biophysica acta Medium 19232372
2011 ZBP-89 physically associates with histone acetyltransferases p300 and Gcn5/Trrap in erythroid cells, and occupies common chromatin sites with Gcn5 within human globin loci. ZBP-89 knockdown results in reduced Gcn5 occupancy, decreased histone H3 acetylation, and lower globin and erythroid-specific gene expression. Co-immunoprecipitation, chromatin immunoprecipitation, lentiviral shRNA knockdown, HDAC inhibitor (valproic acid) rescue Blood High 21828133
2013 ZBP-89 is required for butyrate-induced expression of tryptophan hydroxylase 1 (Tph1) gene in intestinal epithelial enterochromaffin cells. Direct binding of ZBP-89 to the mouse Tph1 promoter was demonstrated by DNA affinity precipitation. Conditional intestinal deletion of ZBP-89 (using VillinCre) abolished butyrate-induced 5-HT production and increased susceptibility to S. typhimurium infection. Conditional knockout mouse (VillinCre × Zfp148(FL/FL)), microarray, DNA affinity precipitation, infection model Gastroenterology High 23395646
2013 ZBP-89 upregulates Bak expression epigenetically by downregulating HDAC3 expression, suppressing HDAC and DNMT activities, maintaining histone acetylation, inhibiting MeCP2 binding, and demethylating CpG islands in the Bak promoter in hepatocellular carcinoma cells. Adenoviral overexpression, HDAC activity assay, DNMT activity assay, chromatin immunoprecipitation, bisulfite sequencing, xenograft mouse model Biochimica et biophysica acta Medium 23954442
2014 Zfp148 deficiency increases p53 activity and reduces atherosclerosis by causing proliferation arrest of lesional macrophages. The anti-atherosclerotic effect of Zfp148 deficiency depends on p53 (epistasis: Zfp148 heterozygosity had no effect on atherosclerosis in Trp53+/- mice). Macrophages from Zfp148(gt/+) mice showed increased phospho-p53. Bone marrow transplantation established the effector cell is hematopoietic. Gene-trap mouse model, bone marrow transplantation, Trp53 epistasis cross, phospho-p53 immunostaining, BrdU proliferation assay Circulation research High 25212213
2014 ZBP-89 directly represses PU.1 transcription and activates SCL/Tal1 and GATA-1 transcription in hematopoietic cells. Conditional deletion of ZBP-89 in adult HSPCs causes transient anemia and thrombocytopenia, and a myeloid-to-B lymphoid lineage switch after bone marrow transplantation, associated with upregulation of PU.1 and downregulation of SCL/Tal1 and GATA-1. Conditional knockout, bone marrow transplantation, chromatin immunoprecipitation, luciferase reporter assay, siRNA in FDCP-Mix A4 cells, flow cytometry Stem cells High 24549639
2015 ZBP-89 attenuates HDAC3 levels by inducing IκB phosphorylation and degradation (independent of NF-κB transcriptional activity), and this process partially depends on Pin1. ZBP-89 forms a complex with IκB. Pin1 knockout cells show significantly less ZBP-89-mediated HDAC3 and IκB reduction. Co-immunoprecipitation, inhibitor studies (CAY10576, MG132, SN50), Pin1 knockout cells, siRNA, adenoviral overexpression, xenograft tumor model Journal of translational medicine Medium 25623232
2016 ZBP-89 drives a feedforward loop of β-catenin expression in colorectal cancer: ZBP-89 binds a site in the proximal CTNNB1 promoter and induces its transcription (identified by ChIP and EMSA). Reciprocally, β-catenin/TCF signaling induces ZNF148 gene expression (TCF sites identified in ZNF148 promoter by ChIP). Conditional deletion of Zfp148 in APC-deleted mice reduces polyp formation. Chromatin immunoprecipitation, EMSA, siRNA, conditional knockout mouse, reporter gene assay Cancer research High 27758879
2017 ZNF148 binds allele-specifically to rs36115365-C in the CLPTM1L/TERT locus at chr5p15.33, confirmed by proteomic pulldown and binding of purified recombinant ZNF148. ZNF148 knockdown reduces TERT expression, telomerase activity, and telomere length. Proteomic binding assay (allele-specific), recombinant protein binding, siRNA knockdown, telomerase activity assay, telomere length measurement Nature communications High 28447668
2019 ZBP-89 negatively regulates liver cancer stem cell (LCSC) self-renewal via inhibition of Notch1 signaling. ZBP-89 localizes in the nucleus with the Notch1 intracellular domain (NICD1) and represses Notch1 signaling by competitively binding NICD1 with MAML1. Exogenous expression, sphere formation assay, co-immunoprecipitation, xenograft mouse model, competitive binding assay Cancer letters Medium 31874246
2019 Zfp148 and its paralog Zfp281 play functionally redundant roles during erythropoiesis. Zfp281 physically associates with GATA-1, occupies common chromatin sites with GATA-1 and Zfp148, and combined deficiency of Zfp148 and Zfp281 causes a marked erythroid maturation block beyond that seen with either alone. Conditional knockout mouse (Zfp148 and Zfp281), co-immunoprecipitation, chromatin immunoprecipitation, flow cytometry, shRNA knockdown Blood advances High 31455666
2019 Zfp148 (along with Klf4 and Klf2) activates autophagy-related genes in smooth muscle cells during aortic aneurysm formation. Zfp148 siRNA inhibits activation of autophagy genes (Beclin, LC3). ChIP demonstrates Zfp148 binds autophagy gene loci in smooth muscle cells after elastase treatment. siRNA knockdown, chromatin immunoprecipitation, qPCR, elastase/IL-1β treatment in vitro Physiological reports Medium 31025534
2020 ZNF148 is phosphorylated by ERK at Ser306, and this phosphorylation causes ZNF148 to bind Forkhead box M1 (FOXM1). ZNF148 and FOXM1 form a complex at promoters, where ZNF148 facilitates histone H3 acetylation and FOXM1-mediated Snail transcription, promoting tumor cell invasion in SDHB-deficient GIST. Phosphorylation assay, co-immunoprecipitation, chromatin immunoprecipitation, reporter gene assay, invasion assay Cancer science Medium 32060966
2020 Zfp148 deficiency downregulates cell cycle genes in mouse embryonic fibroblasts in a p53-dependent manner, and this proliferation arrest requires increased expression of ARF. ChIP showed Zfp148 binds the ARF promoter, suggesting direct repression of ARF transcription by Zfp148. Zfp148 deficiency preferentially bound to promoters of transcription factors, suggesting indirect effects also activate ARF and p53. Chromatin immunoprecipitation (ChIP-seq), mouse embryonic fibroblast proliferation assays, p53/ARF genetic epistasis, CRISPR/siRNA screen data analysis Scientific reports Medium 32843651
2022 ZNF148 is a direct transcriptional target repressed by MYC in breast cancer. ZNF148 transcriptionally represses Inhibitor of DNA binding 1 (ID1) and ID3, drivers of cancer stemness. ZNF148 depletion by shRNA and CRISPR/Cas9 increases TNBC cell proliferation and migration. Global transcriptome and chromatin occupancy analyses (ChIP-seq) confirmed ZNF148 occupancy at ID1/ID3 loci. shRNA knockdown, CRISPR/Cas9 deletion, RNA-seq, ChIP-seq, chromatin occupancy analysis Oncogenesis High 36207293
2022 β cell-specific deletion of Zfp148 (β-Zfp148KO) improves glucose-stimulated Ca2+ oscillations and enhances amino acid-induced Ca2+ influx independent of glycolysis (suggesting enhanced PEP cycling). ZNF148 deletion alters expression of enzymes involved in amino acid and intermediary metabolism (SLC3A2, SLC7A8, GLS, GLS2, PSPH, PHGDH, PSAT1, GOT1, PCK2) and enhances insulin secretion in response to L-glutamine. Conditional knockout mouse (β cell-specific Zfp148 deletion), Ca2+ imaging, RNA-seq, proteomics JCI insight High 35603790
2023 ZNF148 reduction in human islets and deletion in SC-β cells enhances insulin secretion. ZNF148 represses S100A16 expression, which prevents translocation of annexin A2 from nucleus to cell membrane. ZNF148 deletion de-represses annexin-S100 complexes involved in insulin vesicle trafficking and exocytosis. siRNA knockdown in human islets, CRISPR/Cas9 deletion in SC-β cells, transcriptomics, insulin secretion assay, subcellular fractionation JCI insight High 37288664
2023 ZNF148 is a transcriptional activator of the wild-type TERT promoter: ZNF148 binds specifically to the WT TERT promoter at position 124 and upregulates TERT transcription and telomerase activity. ZNF148 shows reduced interaction with the -124C>T mutant allele. Identified by proteomics screen for allele-specific binders. Proteomics (allele-specific pulldown), reporter gene assay, telomerase activity assay Genome research Medium 37918959
2023 Zfp148 and Zfp281 control CD4+ T cell thymic development: they promote intrathymic CD4+ T cell differentiation including expression of the CD4+ lineage-committing factor Thpok. In peripheral TH2 cells, Zfp148 promotes chromatin opening at and expression of TH2 cytokine genes but not of Gata3. Zfp281 physically interacts with Gata3 and is recruited to Gata3 genomic binding sites at Thpok and TH2 cytokine loci. Genetic conditional knockout, single-cell RNA-seq, spatial transcriptomics, co-immunoprecipitation (Zfp281-Gata3), ATAC-seq Science immunology High 37948511
2024 ZNF148 inhibits HBV replication by binding to the RXRα promoter and downregulating RXRα transcription. Overexpression of ZNF148 decreases HBV RNAs, HBV core DNA, and cccDNA transcriptional activity. RXRα overexpression or mutation of its ZNF148 binding site abolishes ZNF148's suppressive effect on HBV replication. Dual-luciferase reporter assay, Northern blot, Southern blot, Western blot, overexpression/siRNA knockdown, rcccDNA mouse model Virology journal Medium 38297280
2025 ZNF148 physically binds p63 in head and neck squamous cell carcinoma cells (identified by proteomics, validated by co-immunoprecipitation). p63 and ZNF148 co-occupy a functional transcribed enhancer-derived RNA (eRNA) upstream of the CCND1 gene, controlling its transcription and overexpression of cyclin D1 to promote tumor cell proliferation. This axis is specific to cancer cells and inactive in normal epithelial cells. Proteomics (p63 pulldown), co-immunoprecipitation, chromatin occupancy (ChIP-seq), eRNA reporter assay Proceedings of the National Academy of Sciences of the United States of America High 40623191
2026 ZFP148 is a transcriptional repressor of cytolytic CD8+ T cell effector differentiation. ZFP148 deficiency increases cytolytic effector CD8+ T cells and reduces exhausted T cells during chronic viral infection. Mechanistically, ZFP148 limits chromatin accessibility at effector-driving transcription factor motifs and directly represses expression of KLF2. Conditional ZFP148 ablation synergizes with PD-1 blockade in tumor models. Conditional knockout (Zfp148fl/fl), chronic viral infection model, ATAC-seq, ChIP-seq or CUT&RUN, flow cytometry, syngeneic tumor models, immunotherapy combination Nature immunology High 41896465

Source papers

Stage 0 corpus · 85 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 ZBP-89, a Krüppel-like zinc finger protein, inhibits epidermal growth factor induction of the gastrin promoter. Molecular and cellular biology 119 8943318
2000 Transcription factor ZBP-89 cooperates with histone acetyltransferase p300 during butyrate activation of p21waf1 transcription in human cells. The Journal of biological chemistry 100 10899165
2001 ZBP-89 promotes growth arrest through stabilization of p53. Molecular and cellular biology 96 11416144
2003 Heterozygosity with respect to Zfp148 causes complete loss of fetal germ cells during mouse embryogenesis. Nature genetics 78 12524542
1998 Transcription factor ZBP-89 regulates the activity of the ornithine decarboxylase promoter. The Journal of biological chemistry 76 9685330
2008 Identification of ZBP-89 as a novel GATA-1-associated transcription factor involved in megakaryocytic and erythroid development. Molecular and cellular biology 63 18250154
2003 ZBP-89 represses vimentin gene transcription by interacting with the transcriptional activator, Sp1. Nucleic acids research 58 12771217
2009 The transcription factor ZBP-89 suppresses p16 expression through a histone modification mechanism to affect cell senescence. The FEBS journal 56 19583777
2000 The zinc finger repressor, ZBP-89, binds to the silencer element of the human vimentin gene and complexes with the transcriptional activator, Sp1. The Journal of biological chemistry 56 10777586
1999 Human stromelysin gene promoter activity is modulated by transcription factor ZBP-89. FEBS letters 53 10359087
2017 Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148. Nature communications 52 28447668
2000 PTRF (polymerase I and transcript-release factor) is tissue-specific and interacts with the BFCOL1 (binding factor of a type-I collagen promoter) zinc-finger transcription factor which binds to the two mouse type-I collagen gene promoters. The Biochemical journal 49 10727401
2004 ZBP-89-induced apoptosis is p53-independent and requires JNK. Cell death and differentiation 47 14963412
2013 ZBP-89 regulates expression of tryptophan hydroxylase I and mucosal defense against Salmonella typhimurium in mice. Gastroenterology 44 23395646
2003 Mutation of p53 in recurrent hepatocellular carcinoma and its association with the expression of ZBP-89. The American journal of pathology 44 12759240
1997 Overexpression of ZBP-89, a zinc finger DNA binding protein, in gastric cancer. Biochemical and biophysical research communications 41 9144414
2010 Transcription factor ZBP-89 in cancer growth and apoptosis. Biochimica et biophysica acta 36 20230874
2014 Loss of one copy of Zfp148 reduces lesional macrophage proliferation and atherosclerosis in mice by activating p53. Circulation research 35 25212213
2000 Three zinc finger nuclear proteins, Sp1, Sp3, and a ZBP-89 homologue, bind to the cyclic adenosine monophosphate-responsive sequence of the bovine adrenodoxin gene and regulate transcription. Biochemistry 35 10757983
2019 Klf4, Klf2, and Zfp148 activate autophagy-related genes in smooth muscle cells during aortic aneurysm formation. Physiological reports 30 31025534
2019 ZBP-89 negatively regulates self-renewal of liver cancer stem cells via suppression of Notch1 signaling pathway. Cancer letters 30 31874246
2003 Transcription factor ZBP-89 is required for STAT1 constitutive expression. Nucleic acids research 30 14654702
2002 The zinc finger transcription factor ZBP-89 is a repressor of the human beta 2-integrin CD11b gene. Blood 30 12393719
1997 ZBP-89, a Krüppel-type zinc finger protein, inhibits cell proliferation. Biochemical and biophysical research communications 29 9268691
2011 Role of ZBP-89 in human globin gene regulation and erythroid differentiation. Blood 28 21828133
2006 The transcription factor ZBP-89 controls generation of the hematopoietic lineage in zebrafish and mouse embryonic stem cells. Development (Cambridge, England) 27 16914492
2007 Sumoylation-dependent control of homotypic and heterotypic synergy by the Kruppel-type zinc finger protein ZBP-89. The Journal of biological chemistry 25 17940278
2016 Truncating de novo mutations in the Krüppel-type zinc-finger gene ZNF148 in patients with corpus callosum defects, developmental delay, short stature, and dysmorphisms. Genome medicine 24 27964749
2009 NF-kappaB and ZBP-89 regulate MMP-3 expression via a polymorphic site in the promoter. Biochemical and biophysical research communications 24 19275880
2006 Recruitment of ataxia-telangiectasia mutated to the p21(waf1) promoter by ZBP-89 plays a role in mucosal protection. Gastroenterology 24 16952553
2006 Intestinal overexpression of ZNF148 suppresses ApcMin/+ neoplasia. Mammalian genome : official journal of the International Mammalian Genome Society 24 17019648
2016 Transcription Factor ZBP-89 Drives a Feedforward Loop of β-Catenin Expression in Colorectal Cancer. Cancer research 23 27758879
2006 An isoform of ZBP-89 predisposes the colon to colitis. Nucleic acids research 21 16517939
2005 A PDGFRA promoter polymorphism, which disrupts the binding of ZNF148, is associated with primitive neuroectodermal tumours and ependymomas. Journal of medical genetics 21 15635072
2002 Regulation of epithelial cell growth by ZBP-89: potential relevance in pancreatic cancer. International journal of gastrointestinal cancer 21 12622418
2011 Thyroid transcription factor-1 (TTF-1) gene: identification of ZBP-89, Sp1, and TTF-1 sites in the promoter and regulation by TNF-α in lung epithelial cells. American journal of physiology. Lung cellular and molecular physiology 20 21784970
2010 ZBP-89 enhances Bak expression and causes apoptosis in hepatocellular carcinoma cells. Biochimica et biophysica acta 20 20850481
2007 ATM phosphorylates ZBP-89 at Ser202 to potentiate p21waf1 induction by butyrate. Biochemical and biophysical research communications 20 17560543
2017 ZNF148 modulates TOP2A expression and cell proliferation via ceRNA regulatory mechanism in colorectal cancer. Medicine 19 28072746
2009 ZBP-89 reduces the cell death threshold in hepatocellular carcinoma cells by increasing caspase-6 and S phase cell cycle arrest. Cancer letters 19 19362768
2013 Epigenetic upregulation of Bak by ZBP-89 inhibits the growth of hepatocellular carcinoma. Biochimica et biophysica acta 18 23954442
2009 Over-expression of the transcription factor, ZBP-89, leads to enhancement of the C2C12 myogenic program. Biochimica et biophysica acta 18 19232372
2001 Retinoic acid (RA) receptor transcriptional activation correlates with inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced ornithine decarboxylase (ODC) activity by retinoids: a potential role for trans-RA-induced ZBP-89 in ODC inhibition. International journal of cancer 18 11149424
2017 MicroRNA-20b suppresses the expression of ZFP-148 in viral myocarditis. Molecular and cellular biochemistry 17 28247213
2012 Promoter cloning and characterization of the human programmed cell death protein 4 (pdcd4) gene: evidence for ZBP-89 and Sp-binding motifs as essential Pdcd4 regulators. Bioscience reports 17 22111549
2023 Upregulation of the ZNF148/PTX3 axis promotes malignant transformation of dendritic cells in glioma stem-like cells microenvironment. CNS neuroscience & therapeutics 16 37063077
2022 A MYC-ZNF148-ID1/3 regulatory axis modulating cancer stem cell traits in aggressive breast cancer. Oncogenesis 16 36207293
2013 Zfp148 deficiency causes lung maturation defects and lethality in newborn mice that are rescued by deletion of p53 or antioxidant treatment. PloS one 16 23405202
2012 Interaction between ZBP-89 and p53 mutants and its contribution to effects of HDACi on hepatocellular carcinoma. Cell cycle (Georgetown, Tex.) 15 22214764
2017 ZBP-89 function in colonic stem cells and during butyrate-induced senescence. Oncotarget 14 29212231
2001 Conserved structure and promoter sequence similarity in the mouse and human genes encoding the zinc finger factor BERF-1/BFCOL1/ZBP-89. Biochemical and biophysical research communications 14 11322790
2018 Regulation between two alternative splicing isoforms ZNF148FL and ZNF148ΔN, and their roles in the apoptosis and invasion of colorectal cancer. Pathology, research and practice 13 30463804
2009 The transcriptional repressor ZBP-89 and the lack of Sp1/Sp3, c-Jun and Stat3 are important for the down-regulation of the vimentin gene during C2C12 myogenesis. Differentiation; research in biological diversity 13 19505630
2021 Loss of microRNA-147 function alleviates synovial inflammation through ZNF148 in rheumatoid and experimental arthritis. European journal of immunology 12 33864383
2018 ZBP-89 and Sp1 contribute to Bak expression in hepatocellular carcinoma cells. BMC cancer 12 29653560
2016 Zinc-binding protein-89 (ZBP-89) cooperates with NF-κB to regulate expression of matrix metalloproteinases (MMPs) in response to inflammatory cytokines. Biochemical and biophysical research communications 12 26891870
2022 A positive feedback loop between tryptophan hydroxylase 1 and β-Catenin/ZBP-89 signaling promotes prostate cancer progression. Frontiers in oncology 11 36172162
2016 Targeting Zfp148 activates p53 and reduces tumor initiation in the gut. Oncotarget 11 27487143
2006 Identification of zinc finger binding protein 89 (ZBP-89) as a transcriptional activator for a major bovine growth hormone receptor promoter. Molecular and cellular endocrinology 11 16621236
2023 Identification of the MALAT1/miR-106a-5p/ZNF148 feedback loop in regulating HaCaT cell proliferation, migration and apoptosis. Regenerative medicine 9 36710662
2023 Zfp281 and Zfp148 control CD4+ T cell thymic development and TH2 functions. Science immunology 9 37948511
2020 Genomic profiling of the transcription factor Zfp148 and its impact on the p53 pathway. Scientific reports 9 32843651
2019 Zfp281 (ZBP-99) plays a functionally redundant role with Zfp148 (ZBP-89) during erythroid development. Blood advances 9 31455666
2014 Stress hematopoiesis is regulated by the Krüppel-like transcription factor ZBP-89. Stem cells (Dayton, Ohio) 9 24549639
2008 ZBP-89 and Sp3 down-regulate while NF-Y up-regulates SOX18 promoter activity in HeLa cells. Molecular biology reports 9 18496767
2022 β Cell-specific deletion of Zfp148 improves nutrient-stimulated β cell Ca2+ responses. JCI insight 8 35603790
2017 Transcription factor ZNF148 is a negative regulator of human muscle differentiation. Scientific reports 8 28811660
1998 The gene encoding the transcriptional repressor BERF-1 maps to a region of conserved synteny on mouse chromosome 16 and human chromosome 3 and a related pseudogene maps to mouse chromosome 8. Cytogenetics and cell genetics 8 9925940
2020 Upregulation of ZNF148 in SDHB-deficient gastrointestinal stromal tumor potentiates Forkhead box M1-mediated transcription and promotes tumor cell invasion. Cancer science 7 32060966
2018 Targeting ZBP-89 for the treatment of hepatocellular carcinoma. Expert opinion on therapeutic targets 7 30142986
2024 ZNF148 inhibits HBV replication by downregulating RXRα transcription. Virology journal 6 38297280
2009 Expression of transcription factor zinc-binding protein-89 (ZBP-89) is inhibited by inflammatory cytokines. Pathology and laboratory medicine international 6 20686646
2006 P53 mutants suppress ZBP-89 function. Anticancer research 6 16827139
2025 p63 and ZNF148 cooperate to regulate head and neck squamous cell carcinoma. Proceedings of the National Academy of Sciences of the United States of America 5 40623191
2022 Novel de novo ZNF148 truncating variant causing autism spectrum disorder, attention deficit hyperactivity disorder, and intellectual disability. Clinical genetics 5 36444493
2024 Further delineation of the rare GDACCF (global developmental delay, absent or hypoplastic corpus callosum, dysmorphic facies syndrome): genotype and phenotype of 22 patients with ZNF148 mutations. Journal of medical genetics 3 37580113
2023 Loss of ZNF148 enhances insulin secretion in human pancreatic β cells. JCI insight 3 37288664
2023 E4F1 and ZNF148 are transcriptional activators of the -57A > C and wild-type TERT promoter. Genome research 3 37918959
2018 Differential Regulation of Zfp30 Expression in Murine Airway Epithelia Through Altered Binding of ZFP148 to rs51434084. G3 (Bethesda, Md.) 3 29242385
2015 ZBP-89 reduces histone deacetylase 3 by degrading IkappaB in the presence of Pin1. Journal of translational medicine 3 25623232
2026 The ZNF148-ZEB1-AS1-IGF2BP2-NOD2 Axis Drives Microglial Antipneumococcal Immunity in Bacterial Meningitis. Glia 2 41457142
2025 Hsa_circRNA_0101125 Promotes Proliferation, Migration, and Invasion of Esophageal Squamous Cell Carcinoma via miR-143-3p/ZNF148 Axis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2 41020579
2026 ZFP148 is a transcriptional repressor of cytolytic effector CD8+ T cell differentiation. Nature immunology 0 41896465
2024 A novel 3q interstitial deletion including GATA2 and ZNF148: A case report. American journal of medical genetics. Part A 0 38567931
2023 A Combination of BRAF and EZH1/SPOP/ZNF148 Three-Gene Mutational Classifier Improves Benign Call Rate in Indeterminate Thyroid Nodules. Endocrine pathology 0 37572175

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