Affinage

MZF1

Myeloid zinc finger 1 · UniProt P28698

Length
734 aa
Mass
82.1 kDa
Annotated
2026-04-29
77 papers in source corpus 48 papers cited in narrative 48 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MZF1 is a myeloid-lineage-enriched C2H2 zinc-finger transcription factor that functions as a context-dependent transcriptional activator or repressor, governing hematopoietic differentiation, oncogene-induced senescence, epithelial-mesenchymal transition, iron homeostasis, and metabolic reprogramming. It contains two independent DNA-binding domains (zinc fingers 1–4 and 5–13) recognizing distinct G-rich consensus sequences, and a SCAN domain that forms domain-swapped homodimers and mediates heterodimerization with partners such as RAZ1 and Elk-1; CK2 phosphorylation at S27 stabilizes the protein, FTO-dependent m6A demethylation stabilizes its mRNA, and SUMO1 modification enables formation of PML-NB-associated nuclear bodies (PMID:8114711, PMID:16950398, PMID:29540671, PMID:29842885, PMID:39954358). Mzf1 knockout mice develop lethal myeloid neoplasias, establishing MZF1 as a hematopoietic tumor suppressor, yet ectopic overexpression transforms fibroblasts and promotes tumorigenesis, reflecting its dual oncogenic and tumor-suppressive roles depending on cellular context (PMID:11445537, PMID:7627970). MZF1 directly regulates a broad target gene repertoire—including CD34, c-myb, CDKN2A/p16INK4A, N-cadherin, PKCα, ferroportin, c-MYC, IGF-IR, and TRPV1—through which it controls processes ranging from granulopoiesis and senescence to EMT, proline and glycolytic metabolism, and neuropathic pain (PMID:7579328, PMID:34773072, PMID:25884514, PMID:31582966, PMID:32042322).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1991 High

    Identification of MZF1 as a myeloid-enriched 13-zinc-finger transcription factor established the gene's tissue-specific expression pattern and structural framework, answering what kind of regulatory protein it encodes.

    Evidence cDNA library screening, Northern blot, and chromosomal mapping in myeloid cell lines

    PMID:1860835

    Open questions at the time
    • No DNA-binding specificity or target genes identified
    • Protein function unknown beyond structural prediction
  2. 1991 Medium

    Antisense inhibition of MZF1 blocked granulocyte colony formation, providing the first functional evidence that MZF1 is required for myeloid differentiation.

    Evidence Antisense oligonucleotide treatment of G-CSF-driven colony assays

    PMID:1719120

    Open questions at the time
    • Antisense approach lacks modern specificity controls
    • Target genes mediating the differentiation effect unknown
  3. 1994 High

    Defining two independent DNA-binding domains with distinct G-rich consensus sequences resolved how MZF1 recognizes DNA and explained its capacity to regulate diverse promoters.

    Evidence SELEX from degenerate oligonucleotide libraries and EMSA with purified recombinant domains

    PMID:8114711

    Open questions at the time
    • No in vivo target gene validation
    • Structural basis of DNA recognition not yet determined
  4. 1995 High

    Demonstrating that MZF1 acts as an activator in hematopoietic cells but a repressor in non-hematopoietic cells on the same CD34 promoter established MZF1's context-dependent bifunctionality, while overexpression-induced transformation of NIH 3T3 cells revealed its oncogenic potential.

    Evidence Reporter assays across multiple cell types; retroviral overexpression with focus formation and nude mouse tumorigenesis

    PMID:7565760 PMID:7579328 PMID:7627970

    Open questions at the time
    • Cofactors determining activator vs. repressor switch unidentified
    • Mechanism of transformation not molecularly defined
  5. 2000 High

    Discovery that the SCAN domain mediates homodimerization and heterodimerization with RAZ1 revealed MZF1's capacity for combinatorial protein-protein interactions beyond DNA binding.

    Evidence Yeast two-hybrid screen of bone marrow library followed by reciprocal co-immunoprecipitation

    PMID:10777584

    Open questions at the time
    • Functional consequence of RAZ1 interaction on transcription unknown
    • Full repertoire of SCAN-mediated partners not mapped
  6. 2001 High

    Mzf1 knockout mice developing lethal myeloid neoplasias resolved the paradox of MZF1's dual nature by proving it functions as a tumor/growth suppressor in the hematopoietic compartment in vivo.

    Evidence Gene-targeted Mzf1−/− mice with histopathology and hematopoietic colony/long-term culture assays

    PMID:11445537

    Open questions at the time
    • Direct transcriptional targets mediating tumor suppression not identified
    • Whether overexpression transforms hematopoietic cells in vivo not tested
  7. 2005 High

    Identification of an NF-Y/MZF1/GATA-2 enhancer complex at the ERV-9 LTR and MZF1's activation of N-cadherin and PKCα broadened the target gene repertoire beyond hematopoiesis into bone biology and hepatocellular carcinoma.

    Evidence EMSA, co-IP, ChIP, and reporter mutagenesis in osteoblasts, K562, and HCC cells

    PMID:15541732 PMID:16105833 PMID:16297876

    Open questions at the time
    • In vivo relevance of NF-Y/MZF1/GATA-2 complex for globin expression not shown
    • How MZF1 selects targets in different tissues unclear
  8. 2006 High

    NMR structure of the SCAN domain homodimer revealed a domain-swapped architecture with ~600 nM affinity, providing the first atomic-resolution view of MZF1's dimerization interface.

    Evidence NMR spectroscopy with GST pull-down and tryptophan fluorescence polarization

    PMID:16950398

    Open questions at the time
    • Structure of zinc-finger domains bound to DNA not solved
    • How SCAN dimerization modulates transcriptional output unknown
  9. 2015 High

    Mapping the MZF1–Elk-1 heterodimer interface (MZF1 acidic domain–Elk-1 heparin-binding domain) and showing that peptide disruption suppresses PKCα-driven EMT and tumorigenesis established a druggable protein-protein interaction axis.

    Evidence Co-IP, Re-ChIP, domain-mapping, peptide interference, and functional rescue in breast cancer and HCC cells

    PMID:26010542 PMID:27542222

    Open questions at the time
    • In vivo pharmacokinetics and specificity of blocking peptides not characterized
    • Whether Elk-1 interaction is required for all MZF1 oncogenic programs unknown
  10. 2018 High

    CK2 phosphorylation at S27 was shown to stabilize MZF1 protein and drive N-cadherin-dependent EMT, while FTO-mediated m6A demethylation was shown to stabilize MZF1 mRNA, together revealing two layers of post-transcriptional/post-translational MZF1 regulation.

    Evidence Phosphorylation site mapping with kinase co-IP (CK2); FTO catalytic mutant with m6A quantification and mRNA stability assay

    PMID:29540671 PMID:29842885

    Open questions at the time
    • Other phosphorylation sites and kinases not systematically surveyed
    • Whether CK2 and FTO pathways converge in the same tumor context unknown
  11. 2019 High

    The lncRNA MZF1-AS1 was found to recruit PARP1 to E2F1, driving MZF1 transcription and downstream proline synthesis, while MZF1 in dorsal root ganglia was linked to TRPV1-dependent neuropathic pain, greatly expanding MZF1's functional scope beyond cancer.

    Evidence RNA pulldown, co-IP, ChIP, metabolic flux in neuroblastoma; viral overexpression/siRNA in rat DRG with behavioral pain testing

    PMID:31582966 PMID:31592410

    Open questions at the time
    • Whether MZF1-AS1/PARP1 mechanism operates outside neuroblastoma not tested
    • Direct MZF1 binding to TRPV1 promoter not confirmed by ChIP
  12. 2021 High

    MZF1 was placed in the oncogene-induced senescence pathway: oncogenic Ras activates MZF1 via c-Jun/Ets1, and MZF1 recruits CHD7 chromatin remodeler to drive p16INK4A transcription, explaining how MZF1 can act as a tumor suppressor in primary cells.

    Evidence ChIP for MZF1 and CHD7 at CDKN2A promoter, signaling pathway inhibitors, multiple primary human cell types

    PMID:34773072

    Open questions at the time
    • Whether MZF1-CHD7 interaction is direct or indirect not established
    • How cells escape MZF1-driven senescence during malignant transformation not addressed
  13. 2023 Medium

    Discovery that MZF1 promotes PD-L1 ubiquitination via CDK4 interaction linked MZF1 to immune evasion, suggesting MZF1 modulates the tumor immune microenvironment in hepatocellular carcinoma.

    Evidence Co-IP (MZF1-CDK4), ubiquitination assay, orthotopic and hydrodynamic HCC mouse models with CDK4 inhibitor

    PMID:38074509

    Open questions at the time
    • Mechanism by which MZF1 promotes PD-L1 ubiquitination is indirect and incompletely defined
    • Not independently replicated
    • Whether this applies to other tumor types unknown
  14. 2025 Medium

    Identification of SUMO1-modified MZF1 nuclear bodies associated with PML-NBs expanded MZF1's biology into subnuclear compartmentalization and stress response.

    Evidence Live-cell imaging, immunofluorescence, SUMOylation assay, and proteomic interactome in PC-3 cells

    PMID:39954358

    Open questions at the time
    • Functional consequence of MZF1-NB formation for transcription not tested
    • SUMOylation sites not mapped
    • Whether MZF1-NBs form in non-cancer cells unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: (1) the structural basis of zinc-finger domain–DNA recognition, (2) the molecular determinants that switch MZF1 between activator and repressor modes in different cell types, and (3) whether MZF1's tumor-suppressive (senescence/p16) and oncogenic (EMT/MYC) programs are cell-type exclusive or coexist with context-dependent dominance.
  • No crystal/cryo-EM structure of zinc-finger–DNA complex
  • No genome-wide binding map (ChIP-seq) in primary hematopoietic cells
  • Cofactor code determining activator vs. repressor behavior not systematically defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 10 GO:0140110 transcription regulator activity 10
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-74160 Gene expression (Transcription) 9 R-HSA-1643685 Disease 6 R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-5357801 Programmed Cell Death 4
Partners
CDK4CHD7CSNK2A1ELK1GATA2NFYASETD8STUB1
Complex memberships
MZF1 SCAN homodimerMZF1/Elk-1 heterodimerNF-Y/MZF1/GATA-2 enhancer complex

Evidence

Reading pass · 48 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 MZF1 contains two independent DNA-binding domains (zinc fingers 1–4 and 5–13) that each recognize distinct but related G-rich consensus sequences (1–4: 5'-AGTGGGGA-3'; 5–13: 5'-CGGGnGAGGGGGAA-3'), as determined by affinity selection from degenerate oligonucleotide libraries and gel-shift assays with purified recombinant protein. SELEX/affinity selection from degenerate oligonucleotide library, gel-shift (EMSA) with purified recombinant protein domains Molecular and cellular biology High 8114711
1991 MZF1 is preferentially expressed in myeloid cells (highest in HL-60 cells induced with retinoic acid) and encodes a protein with 13 C2H2 zinc fingers arranged in two domains separated by a glycine-proline-rich region, localised to chromosome 19q13.2-4. cDNA library screening, sequence analysis, Northern blot, chromosomal mapping The Journal of biological chemistry High 1860835
1991 MZF-1 antisense (but not sense) oligonucleotides significantly inhibited G-CSF-driven granulocyte colony formation in vitro, demonstrating a required role for MZF-1 in granulopoiesis. Antisense oligonucleotide inhibition of granulocyte colony formation in vitro The Journal of experimental medicine Medium 1719120
1995 MZF1 acts as a bifunctional transcriptional regulator of the CD34 promoter: it represses transcription in non-hematopoietic cell lines (NIH 3T3, 293) and activates transcription in hematopoietic cell lines (K562, Jurkat), with activation dependent on intact MZF1 binding sites in the CD34 promoter. GAL4 fusion cotransfection reporter assay (CAT/luciferase), EMSA with recombinant MZF1, site-directed mutagenesis of binding sites Blood High 7579328
1995 Constitutive MZF1 overexpression in embryonic stem cells inhibits hematopoietic commitment and prevents induced expression of CD34 and c-myb; MZF1 binds MZF1 consensus sites in the CD34 and c-myb promoters and represses their transcriptional activity in co-transfection assays. Retroviral/stable transfection into ES cells, EMSA with recombinant MZF1, CAT reporter assay, RT-PCR Molecular and cellular biology High 7565760
1995 Retroviral overexpression of MZF-1 in NIH 3T3 fibroblasts causes loss of contact inhibition, loss of substrate dependence, more rapid cell cycling, and formation of aggressive tumors in athymic mice, establishing MZF-1 as an oncogene when aberrantly expressed. Retroviral transduction, focus formation assay, nude mouse tumorigenesis assay Cancer research High 7627970
1995 The human MZF-1 gene is intronless, spans ~3 kb, is a single-copy gene, and its promoter contains retinoic acid response elements and GM-CSF-responsive sequences that drive transcriptional responsiveness; MZF-1 can also auto-regulate its own expression via consensus zinc finger binding sites in its promoter. Genomic cloning, PCR, primer extension, CAT reporter assay with deletion constructs, retroviral overexpression in K562 cells Biochemistry Medium 8845378
1996 Retroviral overexpression of MZF-1 in IL-3-dependent FDCP.1 cells inhibits apoptosis upon IL-3 withdrawal and confers tumorigenic potential in vivo, showing MZF-1 promotes cell survival and oncogenesis in a hematopoietic context. Retroviral transduction, apoptosis assay upon cytokine withdrawal, syngeneic mouse tumor formation assay Leukemia Medium 8667641
1998 Overexpression of MZF-1 in HL-60 cells delays retinoic acid-induced apoptosis and differentiation, sustains proliferation (higher S-phase fraction), reduces CD18 expression after 6 days RA, and is associated with prolonged bcl-2 expression; MZF-1 had no effect on PMA-induced monocyte/macrophage differentiation. Retroviral transduction/overexpression in HL-60 cells, TUNEL, DNA fragmentation, flow cytometry, Western blot for bcl-2 Leukemia High 9593266
2000 The SCAN box (leucine-rich domain) present only in the MZF1B isoform mediates homo- and heterodimeric protein-protein interactions: MZF1B self-associates via its SCAN box and binds the novel SCAN-related protein RAZ1 (identified by yeast two-hybrid screening of a bone marrow library), as confirmed by co-immunoprecipitation. Yeast two-hybrid screen, co-immunoprecipitation, in vitro association assay The Journal of biological chemistry High 10777584
2001 Gene-targeted Mzf1-/- mice develop lethal myeloid neoplasias with liver infiltration by chloroma-like myeloid cells, and Mzf1-/- hematopoietic progenitors show striking increases in autonomous proliferation and long-term hematopoietic capacity, demonstrating that Mzf1 acts as a tumor/growth suppressor in the hematopoietic compartment. Gene targeting (knockout mouse), histopathology, hematopoietic colony and long-term culture assays Genes & development High 11445537
2005 MZF1 binds to a GA-rich core element in the N-cadherin proximal promoter in osteoblasts (identified by EMSA/supershift); cotransfection shows MZF1 overexpression increases N-cadherin promoter activity and N-cadherin mRNA expression, while Sp1/MZF1 together further enhance this effect. EMSA with osteoblast nuclear extracts and competition/supershift assays, deletion/mutation analysis, cotransfection luciferase reporter assay, RT-PCR Experimental cell research Medium 15541732
2005 MZF1 is part of a novel LTR enhancer complex NF-Y/MZF1/GATA-2 at the ERV-9 LTR upstream of the beta-globin locus: NF-Y bound at CCAAT motifs recruits MZF1 (via protein-protein interaction) and GATA-2 to neighboring GTGGGGA and GATA sites; mutation of the CCAAT motif abolishes NF-Y binding and silences downstream gene transcription. EMSA, co-IP/protein-protein interaction assays, chromatin structure analysis, stable reporter assay in K562 cells with promoter mutation The Journal of biological chemistry High 16105833
2005 MZF-1 transcriptionally activates PKCα expression in poorly differentiated HCC cells; antisense MZF-1 oligonucleotides reduce both MZF-1 and PKCα mRNA levels and decrease cell proliferation, migration, and invasion. Antisense oligonucleotide knockdown, RT-PCR, antisense vs. sense oligonucleotide controls, migration/invasion assays, EMSA for promoter binding Biochemical and biophysical research communications Medium 16297876
2005 MZF-1 interacts with the apoptosis-inducing leucine-zipper protein LDOC1 and enhances LDOC1-mediated apoptosis, as shown by co-immunoprecipitation and functional apoptosis assays. Co-immunoprecipitation, phosphatidylserine externalization assay, mitochondrial membrane potential assay, caspase-3 activity assay FEBS letters Medium 15670815
2006 MZF1 binds to a MZF1-like site in the ERCC1 promoter (EMSA with consensus oligonucleotides) and overexpression of MZF1 represses ERCC1 promoter activity; cisplatin treatment decreases MZF1 mRNA and binding activity, coinciding with increased AP1 binding and ERCC1 upregulation. EMSA, CAT reporter cotransfection assay, quantitative PCR Biochemical pharmacology Medium 16426580
2006 The MZF1 SCAN domain forms a domain-swapped homodimer with a Kd ~600 nM; residues from helix 3 compose the core dimer interface; the structure was determined by NMR spectroscopy and validated by GST pull-down self-association assays. NMR structure determination, GST pull-down, tryptophan fluorescence polarization Kd measurement Journal of molecular biology High 16950398
2007 MZF1 and Sp1/Sp3 bind to the PADI1 (peptidylarginine deiminase type I) promoter in keratinocytes in vivo (confirmed by ChIP); mutation of MZF1 or Sp1 binding sites markedly reduces PADI1 promoter activity, and siRNA knockdown of MZF1 or Sp1 diminishes PADI1 expression in both low- and high-calcium conditions. Luciferase reporter with deletion/mutation constructs, ChIP assay, siRNA knockdown, qRT-PCR The Journal of investigative dermatology High 17851584
2009 MZF-1 transcriptionally activates the FGF-2 promoter in striatal astrocytes in response to apomorphine (D1/D2 receptor agonist): a cis-element in the -785/-745 region of the FGF-2 promoter is recognized by MZF-1, and MZF-1 overexpression increases FGF-2 protein levels while MZF-1 siRNA reduces promoter activity. Promoter deletion/reporter assay, EMSA, MZF-1 plasmid overexpression and siRNA knockdown, FGF-2 protein quantification Journal of neurochemistry Medium 19196427
2012 MZF1 transcriptionally activates the p55PIK (regulatory subunit of PI3K) gene by directly binding to the TGGGGA cis-element in the p55PIK promoter (confirmed by ChIP); MZF1 overexpression increases p55PIK promoter activity and expression, leading to increased colorectal cancer cell proliferation, while MZF1 silencing has the opposite effects. ChIP assay, luciferase reporter assay, MZF1 overexpression/siRNA knockdown, cell proliferation assay BioMed research international Medium 23509792
2014 MZF-1 transcriptionally regulates ferroportin (FPN) expression; increased MZF-1 promotes FPN-driven iron egress, reducing intracellular iron and restraining prostate tumor cell growth, while inhibition of MZF-1 reduces FPN, causes iron retention and enhanced tumor growth. AP4 and c-Myb jointly activate MZF1 transcription, and miR-492 directly inhibits MZF1 via its 3'UTR. siRNA/shRNA knockdown, overexpression, iron assay, xenograft tumor model, luciferase reporter for miR-492 3'UTR binding, qRT-PCR, Western blot Oncogene High 25284586
2014 OPN (osteopontin) induces integrin-dependent MSC expression of TGF-β1, which mediates MSC-to-CAF transformation; this pathway requires MZF1 as a transcription factor, and MZF1/TGF-β1-dependent CAF transformation promotes tumor growth and metastasis in xenograft models. In vitro co-culture with human MSCs and breast cancer lines, in vivo xenograft in NOD-scid mice, loss-of-function with siRNA/shRNA for MZF1 and TGF-β1, tumor growth/metastasis readouts Oncogene High 25531323
2014 LKB1 loss leads to increased MZF1 expression, which in turn drives MYC transcription; the MZF1/MYC axis mediates soft-agar growth, migration, and invasion in lung adenocarcinoma cells, and MYC inhibitors suppress LKB1-loss-induced invasiveness. shRNA knockdown of LKB1/MZF1, luciferase reporter for MYC promoter, MYC inhibitor treatment, soft-agar and invasion assays Oncogene Medium 24793789
2014 MZF1 directly binds the SMAD4 promoter core region (confirmed by EMSA and luciferase reporter with mutations) and activates SMAD4 transcription; MZF1 expression reduces migration of gastric adenocarcinoma cells, establishing an MZF1-SMAD4 tumor-suppressive axis. EMSA, luciferase reporter with site-directed mutagenesis, ChIP, wound-healing/Transwell migration assay International journal of oncology Medium 27922669
2014 MZF1 is required for FOXM1 upregulation by HPV E6 oncoprotein through the MZF1/NKX2-1 axis; NKX2-1 induced by E6 drives MZF1-mediated transcription of FOXM1, which activates Wnt/β-catenin signaling to promote tumor aggressiveness, invasiveness, and stemness. shRNA knockdown of E6/MZF1/FOXM1, luciferase reporter, nude mouse metastasis model, FOXM1 inhibitor (thiostrepton) Neoplasia Medium 25425970
2015 MZF1 and Elk-1 form a heterodimeric complex that binds the PKCα promoter; Elk-1 binds the N-terminal region of MZF1 and MZF1 binds the C-terminal region of Elk-1 (confirmed by Co-IP, Re-ChIP); DNA-binding-deficient mutants of either factor reduce PKCα expression, cell proliferation, migration, invasion, and tumorigenicity in HCC. Co-IP, ChIP, Re-ChIP, luciferase reporter with DNA-binding-deficient mutants, migration/invasion/tumorigenicity assays PloS one High 26010542
2015 MZF1 suppresses IGF-IR gene promoter activity in NPM-ALK+ T-cell lymphoma (confirmed by luciferase assay and ChIP); forced MZF1 expression reduces IGF-IR mRNA/protein and downstream pIGF-IR, IRS-1, AKT, and NPM-ALK phosphorylation, and decreases lymphoma cell viability, proliferation, migration, and colony formation. Luciferase reporter assay, ChIP, forced overexpression, Western blot for downstream signaling, viability/proliferation/migration/colony assays Molecular cancer High 25884514
2016 The acidic domain (residues 60–72) of MZF-1 interacts with the heparin-binding domain (residues 145–157) of Elk-1 to form a heterodimer; blocking this interaction with peptide fragments (MZF-160-72 or Elk-1145-157) decreases MZF-1/Elk-1 complex formation, reduces PKCα promoter binding, and suppresses PKCα expression, migration, tumorigenicity, and EMT in triple-negative breast cancer cells. Peptide transfection to block protein-protein interaction, luciferase reporter, ChIP for PKCα promoter binding, rescue by full-length PKCα Oncotarget High 27542222
2016 MZF1 directly binds the mutational landscape of the MZF1 SCAN domain as assessed by NMR-validated conformational ensemble; the SCAN domain mediates homo- and heterodimerization and its cancer-related substitutions perturb the protein-protein interaction network of MZF1. NMR spectroscopy, molecular dynamics simulations, proteomics/RNASeq data analysis Frontiers in molecular biosciences Medium 28018905
2017 TGF-β1 induces CK17 expression in cervical cancer cells via the ERK1/2-MZF1 signaling pathway; ERK1/2 inhibitors block CK17 induction, and MZF1 directly binds the CK17 promoter as identified and validated by combined computational and experimental approaches; CK17 promotes cancer stem cell properties and lymphatic metastasis without inducing EMT. ERK1/2 inhibitor treatment, MZF1 promoter binding validation (ChIP/EMSA), shRNA knockdown, in vivo metastasis assay The FEBS journal Medium 28703907
2017 MZF1 upregulates PRAME expression via direct binding to intron DNA containing MZF1 binding sites overlapping a CpG-rich region; MZF1 binding is enhanced by DNA demethylation (5-azaC treatment), and MZF1 promotes colony-forming ability in melanoma cells. Luciferase reporter, EMSA, ChIP, 5-azaC treatment, overexpression assay, colony formation assay Cancer letters Medium 28634046
2018 FTO (m6A demethylase) enhances MZF1 mRNA expression in lung squamous cell carcinoma by reducing m6A levels on MZF1 mRNA, thereby increasing MZF1 mRNA stability; FTO knockdown decreases MZF1 expression and inhibits cell proliferation and invasion. m6A quantification, MZF1 mRNA stability assay, FTO knockdown/overexpression (including catalytic mutant), cell proliferation/apoptosis/invasion assays Biochemical and biophysical research communications High 29842885
2018 CK2 directly interacts with MZF1 and phosphorylates it at serine 27, which stabilizes MZF1 protein; phosphorylation-stabilized MZF1 then drives N-cadherin transcription (confirmed by ChIP), promoting EMT, cell motility and invasiveness; MZF1 knockdown reverts cancer cells from mesenchymal to epithelial morphology. Co-IP (direct CK2-MZF1 interaction), phosphorylation site mapping (S27), protein stability assay, ChIP for N-cadherin promoter, morphological analysis, migration/invasion assay Oncogenesis High 29540671
2018 CHIP/STUB1 ubiquitin ligase negatively regulates MZF1 DNA-binding activity in the nucleus; loss of nuclear CHIP unleashes MZF1-driven transcription of cathepsin B/L (CTSB/L), promoting tumor cell invasion and xenograft growth in ErbB2+ breast cancer cells. Unbiased transcription factor activity screen, ectopic CHIP expression, CTSB inhibition, xenograft growth assay Cancer research Medium 29510992
2019 MZF1-AS1 lncRNA binds PARP1 and facilitates PARP1 interaction with E2F1, resulting in E2F1 transactivation and upregulation of MZF1 and other oncogenic genes; MZF1 in turn promotes aldehyde dehydrogenase 18A1 and PYCR1 expression to drive proline synthesis in neuroblastoma; a peptide blocking MZF1-AS1/PARP1 interaction suppresses tumor progression. RNA pulldown, co-IP (PARP1-E2F1), ChIP, luciferase reporter, small peptide blocking, lentiviral shRNA, in vivo tumor assay, amino acid profiling Advanced science High 31592410
2019 Sublytic C5b-9 activates the FBXO28-TRAF6 complex, which promotes K63-ubiquitination and phosphorylation of ERK5; activated ERK5 drives MZF1 expression, which then binds the RGC-32 promoter to upregulate RGC-32, causing glomerular mesangial cell proliferation in rat Thy-1 nephritis. Co-IP (FBXO28-TRAF6-ERK5), ubiquitination assay, ChIP for MZF1 at RGC-32 promoter, luciferase reporter, gene knockdown in vivo (siRNA), histology Journal of cellular and molecular medicine High 31184423
2019 MZF1 in dorsal root ganglia promotes TRPV1 expression (but not P2X7R) and contributes to neuropathic pain; CCI increases MZF1 and TRPV1 in L4/5 DRGs; viral overexpression of MZF1 induces allodynia and hyperalgesia in naïve rats, while MZF1 siRNA ameliorates CCI-induced pain behaviors. rAAV5 viral overexpression of MZF1 in DRG, MZF1 siRNA microinjection, behavioral pain testing (PWT, PWL), Western blot for TRPV1 and P2X7R Neural plasticity Medium 31582966
2019 MZF1 transcriptionally activates the Mtor promoter in a strain-specific manner in mice: a T (vs. C) at -6 relative to Tssr 40273 creates an MZF1 consensus binding site; MZF1 binds this TGGGGA element (confirmed by EMSA, DNA pulldown, and ChIP-PCR) and overexpression of MZF1 reduces Mtor promoter activity more strongly in BALB mice than DBA mice. EMSA, DNA pulldown, ChIP-PCR, luciferase reporter with allelic variants, MZF1 overexpression and Mzf1 knockdown in fibroblasts and plasmacytoma cells The Journal of biological chemistry High 31548308
2020 Linc01060 (lncRNA from hypoxic glioma stem cell exosomes) directly interacts with MZF1 and enhances its protein stability and nuclear translocation, enabling MZF1-mediated c-Myc transcriptional activation; c-Myc then enhances HIF1α accumulation post-transcriptionally; HIF1α feeds back by binding the Linc01060 promoter to upregulate Linc01060 transcription. RNA-protein interaction assay (Linc01060-MZF1), subcellular fractionation (nuclear translocation), co-IP, luciferase reporter (MZF1/c-Myc promoter), ChIP (HIF1α at Linc01060 promoter) Cancer research High 33158815
2020 YY1 transcription factor drives MZF1 transcription; a 21-amino acid upstream open reading frame-encoded peptide (MZF1-uPEP) binds the zinc finger domain of YY1 and represses YY1 transactivation, thereby reducing MZF1 and its downstream glycolytic targets HK2 and PGK1 in neuroblastoma. Dual-luciferase assay, ChIP, Co-IP, mass spectrometry, peptide pull-down, sucrose gradient sedimentation, seahorse metabolic flux, soft agar, in vivo nude mouse assay Theranostics High 32042322
2021 MZF1 mediates oncogene-induced senescence by recruiting CHD7 to the p16INK4A (CDKN2A) promoter to drive p16INK4A transcription; MZF1 expression is itself induced by oncogenic Ras through c-Jun and Ets1 transcription factors activated by the Ras-Raf-1-MEK-ERK signaling pathway. ChIP (MZF1 and CHD7 at p16INK4A promoter), reporter assay, knockdown of MZF1/CHD7, epistasis in primary human cells from multiple origins, signaling pathway inhibitors Oncogene High 34773072
2021 GSK3β mediates ubiquitination of FTO demethylase, reducing FTO expression; this increases m6A modification of MZF1 mRNA, suppressing MZF1 expression and consequently decreasing c-Myc, thereby inhibiting colorectal carcinoma cell proliferation. Ubiquitination assay, m6A methylation assay on MZF1 mRNA, MZF1-FTO interaction assay (co-IP), overexpression/knockdown, in vivo tumor model with c-Myc rescue Journal of cellular and molecular medicine Medium 33533172
2021 Irradiation upregulates MZF1, which transcriptionally represses miR-541-5p (and its primary precursor pri-miR-541-5p); reduced miR-541-5p de-represses Slug, promoting EMT and radiation-induced pulmonary fibrosis; ectopic miR-541-5p mitigates RIPF in vivo. Irradiation model in vitro and in vivo (mouse RIPF), MZF1 knockdown/overexpression, luciferase reporter for miR-541-5p promoter, Slug knockdown, EMT marker analysis International journal of molecular sciences Medium 34768749
2022 SETD8 (histone methyltransferase) and MZF1 co-occupy the WNT5A promoter and cooperate to regulate WNT5A expression in human glomerular endothelial cells; high glucose increases MZF1 expression and decreases SETD8 expression; SETD8 silencing expands MZF1 enrichment on the WNT5A promoter, increasing WNT5A transcription and downstream NF-κB-mediated inflammation. Co-IP (MZF1-SETD8), ChIP (MZF1 and SETD8/H4K20me1 at WNT5A promoter), dual luciferase reporter, siRNA knockdown, immunofluorescence, in vivo DN rat model Cellular & molecular biology letters High 35350980
2023 MZF1 promotes PD-L1 ubiquitination and degradation by binding to the CDK4 activation site; CDK4 directly binds MZF1 and increases MZF1 expression; in turn, elevated MZF1 suppresses T-cell recruitment and confers resistance to anti-PD-L1 immunotherapy in hepatocellular carcinoma. Protein degradation assay, ubiquitination assay, co-IP (MZF1-CDK4), orthotopic and hydrodynamic mouse HCC models, CDK4 inhibitor treatment JHEP reports Medium 38074509
2023 UHRF1/DNMT1 complex hypermethylates an intragenic CpG island (iCpGI) in the PRSS3 gene, interfering with MZF1 binding and suppressing PRSS3-V3 expression; site-specific iCpGI demethylation (by diallyl trisulfide + 5-aza-dC) allows MZF1 to access the PRSS3 promoter and upregulate tumor-suppressive PRSS3-V3 in lung cancer cells. ChIP, luciferase reporter, bisulfite sequencing, co-IP (UHRF1-DNMT1), drug treatment, isoform-specific expression analysis Acta pharmaceutica Sinica B Medium 37250150
2023 SLC1A5-AS lncRNA directly binds MZF1 protein (confirmed by biotin-labeled probe pulldown and western blot), sequestering MZF1 away from the SLC1A5 promoter and relieving MZF1-mediated repression, leading to increased ASCT2 expression and enhanced glutamine uptake in hepatocellular carcinoma. Biotin-labeled RNA probe pulldown (SLC1A5-AS/MZF1 interaction), luciferase reporter, ChIP, Western blot, glutamine uptake assay, in vivo xenograft Discovery medicine Medium 38058065
2025 MZF1 forms intranuclear nuclear bodies (MZF1-NBs) that associate with PML-NBs; MZF1 is SUMO1-SUMOylated in PC-3 cells, enabling interaction with SUMO-interaction motif (SIM)-containing proteins; interactome analysis identifies MZF1-NB participation in stress response (TPR, UBAP2L), protein folding (CALR, ANKRD40), post-translational modification (TRIM33, CAMK2D, CAMK2G), and RNA binding (ALURBP, CPSF5). Live-cell imaging/immunofluorescence (nuclear body identification), proteomic/interactome analysis, SUMOylation assay, protein-protein interaction analysis Biochemical and biophysical research communications Medium 39954358

Source papers

Stage 0 corpus · 77 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 m6A demethylase FTO facilitates tumor progression in lung squamous cell carcinoma by regulating MZF1 expression. Biochemical and biophysical research communications 199 29842885
2014 Osteopontin mediates an MZF1-TGF-β1-dependent transformation of mesenchymal stem cells into cancer-associated fibroblasts in breast cancer. Oncogene 188 25531323
1994 Characterization of the DNA-binding properties of the myeloid zinc finger protein MZF1: two independent DNA-binding domains recognize two DNA consensus sequences with a common G-rich core. Molecular and cellular biology 174 8114711
1991 A retinoic acid-responsive human zinc finger gene, MZF-1, preferentially expressed in myeloid cells. The Journal of biological chemistry 167 1860835
2001 Mzf1 controls cell proliferation and tumorigenesis. Genes & development 112 11445537
2020 Hypoxic Glioma Stem Cell-Derived Exosomes Containing Linc01060 Promote Progression of Glioma by Regulating the MZF1/c-Myc/HIF1α Axis. Cancer research 105 33158815
1995 Overexpression of the zinc finger protein MZF1 inhibits hematopoietic development from embryonic stem cells: correlation with negative regulation of CD34 and c-myb promoter activity. Molecular and cellular biology 105 7565760
1995 The myeloid zinc finger gene, MZF-1, regulates the CD34 promoter in vitro. Blood 96 7579328
1996 Hematopoietic transcriptional regulation by the myeloid zinc finger gene, MZF-1. Current topics in microbiology and immunology 84 8585946
1991 Antisense oligonucleotides from the stage-specific myeloid zinc finger gene MZF-1 inhibit granulopoiesis in vitro. The Journal of experimental medicine 79 1719120
2014 The MZF1/c-MYC axis mediates lung adenocarcinoma progression caused by wild-type lkb1 loss. Oncogene 62 24793789
1995 Aberrant expression of the myeloid zinc finger gene, MZF-1, is oncogenic. Cancer research 60 7627970
2005 Sp1/Sp3 and the myeloid zinc finger gene MZF1 regulate the human N-cadherin promoter in osteoblasts. Experimental cell research 57 15541732
2014 Myeloid zinc-finger 1 (MZF-1) suppresses prostate tumor growth through enforcing ferroportin-conducted iron egress. Oncogene 54 25284586
2005 The long terminal repeat (LTR) of ERV-9 human endogenous retrovirus binds to NF-Y in the assembly of an active LTR enhancer complex NF-Y/MZF1/GATA-2. The Journal of biological chemistry 50 16105833
2005 PKCalpha expression regulated by Elk-1 and MZF-1 in human HCC cells. Biochemical and biophysical research communications 48 16297876
2017 TGF-β1-induced CK17 enhances cancer stem cell-like properties rather than EMT in promoting cervical cancer metastasis via the ERK1/2-MZF1 signaling pathway. The FEBS journal 46 28703907
2000 Identification of a novel SCAN box-related protein that interacts with MZF1B. The leucine-rich SCAN box mediates hetero- and homoprotein associations. The Journal of biological chemistry 46 10777584
1998 The myeloid zinc finger gene (MZF-1) delays retinoic acid-induced apoptosis and differentiation in myeloid leukemia cells. Leukemia 46 9593266
2014 Up-regulation of FOXM1 by E6 oncoprotein through the MZF1/NKX2-1 axis is required for human papillomavirus-associated tumorigenesis. Neoplasia (New York, N.Y.) 44 25425970
2018 Loss of the Nuclear Pool of Ubiquitin Ligase CHIP/STUB1 in Breast Cancer Unleashes the MZF1-Cathepsin Pro-oncogenic Program. Cancer research 40 29510992
2020 Therapeutic targeting of YY1/MZF1 axis by MZF1-uPEP inhibits aerobic glycolysis and neuroblastoma progression. Theranostics 39 32042322
2019 Therapeutic Targeting of MZF1-AS1/PARP1/E2F1 Axis Inhibits Proline Synthesis and Neuroblastoma Progression. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 38 31592410
2012 p55PIK transcriptionally activated by MZF1 promotes colorectal cancer cell proliferation. BioMed research international 38 23509792
2005 LDOC1, a novel MZF-1-interacting protein, induces apoptosis. FEBS letters 38 15670815
2020 Zinc Finger Transcription Factor MZF1-A Specific Regulator of Cancer Invasion. Cells 37 31963147
2021 Kinase GSK3β functions as a suppressor in colorectal carcinoma through the FTO-mediated MZF1/c-Myc axis. Journal of cellular and molecular medicine 35 33533172
2017 Tumor antigen PRAME is up-regulated by MZF1 in cooperation with DNA hypomethylation in melanoma cells. Cancer letters 34 28634046
2006 MZF1 possesses a repressively regulatory function in ERCC1 expression. Biochemical pharmacology 33 16426580
2009 Crucial roles of MZF-1 in the transcriptional regulation of apomorphine-induced modulation of FGF-2 expression in astrocytic cultures. Journal of neurochemistry 29 19196427
2007 Crucial roles of MZF1 and Sp1 in the transcriptional regulation of the peptidylarginine deiminase type I gene (PADI1) in human keratinocytes. The Journal of investigative dermatology 29 17851584
2016 The Mutational Landscape of the Oncogenic MZF1 SCAN Domain in Cancer. Frontiers in molecular biosciences 28 28018905
2021 Irradiation Activates MZF1 to Inhibit miR-541-5p Expression and Promote Epithelial-Mesenchymal Transition (EMT) in Radiation-Induced Pulmonary Fibrosis (RIPF) by Upregulating Slug. International journal of molecular sciences 25 34768749
2007 Suppression of tumorigenicity of human hepatocellular carcinoma cells by antisense oligonucleotide MZF-1. The Chinese journal of physiology 25 17593797
1995 Isolation and functional characterization of the human gene encoding the myeloid zinc finger protein MZF-1. Biochemistry 25 8845378
1996 Forced over-expression of the myeloid zinc finger gene MZF-1 inhibits apoptosis and promotes oncogenesis in interleukin-3-dependent FDCP.1 cells. Leukemia 24 8667641
2015 The transcription factors Ik-1 and MZF1 downregulate IGF-IR expression in NPM-ALK⁺ T-cell lymphoma. Molecular cancer 21 25884514
2015 MZF-1/Elk-1 Complex Binds to Protein Kinase Cα Promoter and Is Involved in Hepatocellular Carcinoma. PloS one 21 26010542
2023 UHRF1/DNMT1-MZF1 axis-modulated intragenic site-specific CpGI methylation confers divergent expression and opposing functions of PRSS3 isoforms in lung cancer. Acta pharmaceutica Sinica. B 20 37250150
2018 Phosphorylation-dependent stabilization of MZF1 upregulates N-cadherin expression during protein kinase CK2-mediated epithelial-mesenchymal transition. Oncogenesis 20 29540671
2006 Structure of the SCAN domain from the tumor suppressor protein MZF1. Journal of molecular biology 20 16950398
2021 MZF1 mediates oncogene-induced senescence by promoting the transcription of p16INK4A. Oncogene 16 34773072
2023 Design and In Silico Validation of a Novel MZF-1-Based Multi-Epitope Vaccine to Combat Metastatic Triple Negative Breast Cancer. Vaccines 15 36992161
2019 Sublytic C5b-9 induces proliferation of glomerular mesangial cells via ERK5/MZF1/RGC-32 axis activated by FBXO28-TRAF6 complex. Journal of cellular and molecular medicine 15 31184423
2016 MZF-1/Elk-1 interaction domain as therapeutic target for protein kinase Cα-based triple-negative breast cancer cells. Oncotarget 15 27542222
2016 Upregulation of SMAD4 by MZF1 inhibits migration of human gastric cancer cells. International journal of oncology 15 27922669
2022 SETD8 cooperates with MZF1 to participate in hyperglycemia-induced endothelial inflammation via elevation of WNT5A levels in diabetic nephropathy. Cellular & molecular biology letters 14 35350980
2023 Asiatic acid exhibits antimetastatic activity in human prostate cancer cells by modulating the MZF-1/Elk-1/Snail signaling axis. European journal of pharmacology 12 37209940
2019 MZF1 in the Dorsal Root Ganglia Contributes to the Development and Maintenance of Neuropathic Pain via Regulation of TRPV1. Neural plasticity 11 31582966
2014 Myeloid zinc finger 1 (Mzf1) differentially modulates murine cardiogenesis by interacting with an Nkx2.5 cardiac enhancer. PloS one 11 25436607
2023 LncRNA SLC1A5-AS/MZF1/ASCT2 Axis Contributes to Malignant Progression of Hepatocellular Carcinoma. Discovery medicine 10 38058065
2023 MZF1 promotes tumour progression and resistance to anti-PD-L1 antibody treatment in hepatocellular carcinoma. JHEP reports : innovation in hepatology 10 38074509
2019 Myeloid Zinc Finger 1 (MZF1) Maintains the Mesenchymal Phenotype by Down-regulating IGF1R/p38 MAPK/ERα Signaling Pathway in High-level MZF1-expressing TNBC cells. Anticancer research 10 31366500
2012 Expression of protein kinase C α and the MZF-1 and Elk-1 transcription factors in human breast cancer cells. The Chinese journal of physiology 10 22242952
1996 The location of MZF-1 at the telomere of human chromosome 19q makes it vulnerable to degeneration in aging cells. Leukemia research 10 8637224
2022 Inhibition of MZF1/c-MYC Axis by Cantharidin Impairs Cell Proliferation in Glioblastoma. International journal of molecular sciences 9 36499054
2005 MZF-1 and DbpA interact with DNase I hypersensitive sites that correlate with expression of the human MUC1 mucin gene. Experimental cell research 9 15893750
2021 MZF1 alleviates oxidative stress and apoptosis induced by rotenone in SH-SY5Y cells by promoting RBM3 transcription. The Journal of toxicological sciences 8 34602532
2019 The transcription factor MZF1 differentially regulates murine Mtor promoter variants linked to tumor susceptibility. The Journal of biological chemistry 8 31548308
2014 The glyceraldehyde 3-phosphate dehydrogenase gene (GAPDH) is regulated by myeloid zinc finger 1 (MZF-1) and is induced by calcitriol. Biochemical and biophysical research communications 8 25065746
2015 Myeloid Zinc Finger 1 (MZF-1) Regulates Expression of the CCN2/CTGF and CCN3/NOV Genes in the Hematopoietic Compartment. Journal of cellular physiology 7 25899830
2012 Expression of protein kinase Cα and the MZF-1 and elk-1 transcription factors in human bladder transitional cell carcinoma cells. The Chinese journal of physiology 7 22559731
2022 MZF1 Transcriptionally Activated MicroRNA-328-3p Suppresses the Malignancy of Stomach Adenocarcinoma via Inhibiting CD44. Journal of immunology research 6 35669102
2022 Axl Expression in Renal Mesangial Cells Is Regulated by Sp1, Ap1, MZF1, and Ep300, and the IL-6/miR-34a Pathway. Cells 6 35740998
2024 Amelioration of nitroglycerin-induced migraine in mice via Wuzhuyu decoction: Inhibition of the MZF1/PGK1 pathway and activation of NRF2 antioxidant response. Journal of ethnopharmacology 5 38373662
2024 MitoAMPK inhibits the Warburg effect by MZF1-SIRT6 with glycosis related genes in NSCLC. Journal of cellular and molecular medicine 5 39224032
2020 Cigarette smoke modulates binding of the transcription factor MZF1 to the VEGF promoter and regulates VEGF expression in dependence of genetic variation SNP 405. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 5 32449233
2013 Haplotype of single nucleotide polymorphisms in exon 6 of the MZF-1 gene and Alzheimer's disease. Journal of Alzheimer's disease : JAD 4 23241556
2024 Solamargine acts as an antiviral by interacting to MZF1 and targeting the core promoter of the hepatitis B virus gene. Aging 2 39133152
2025 Discovery of myeloid zinc finger (MZF) 1 nuclear bodies. Biochemical and biophysical research communications 1 39954358
2025 PRAME-AS lncRNA, regulated by MZF1, modulates PRAME expression and cell stemness. PloS one 0 40961095
2025 FTO-Mediated m6A Demethylation of MZF1 Regulates DECR1 to Promote Fatty Acid Oxidation and Exacerbate Myocardial Ischemia/Reperfusion Injury : FTO-Mediated m6A Demethylation of MZF1 Enhances Fatty Acid Oxidation and Aggravates Myocardial I/R Injury. Biochemical genetics 0 41003915
2025 MicroRNA‑199a‑3p suppresses non‑small cell lung cancer progression by targeting FTO to enhance m6A‑mediated downregulation of MZF1 and its transcriptional activation of CLDND1. Molecular medicine reports 0 41201047
2025 MZF1-AS1/NSUN2 promotes the peritoneal metastasis of gastric cancer by enhancing the stability of RAB13 mRNA. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 0 41343127
2020 RETRACTED: MZF1 regulates α-globin gene transcription via long-range interactions in erythroid differentiation. Blood cells, molecules & diseases 0 33352376
2019 [Effects of Transcription Factor MZF-1 on Transcriptive Regulation of Acute Monocytic Leukemia-related Gene MLAA-34]. Zhongguo shi yan xue ye xue za zhi 0 31607299
2019 Regulation of expression of MLAA-34 gene through transcriptional factors E2F1 and MZF-1. International journal of clinical and experimental pathology 0 31934032