Affinage

TFAP4

Transcription factor AP-4 · UniProt Q01664

Length
338 aa
Mass
38.7 kDa
Annotated
2026-04-28
100 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TFAP4 is a basic helix-loop-helix (bHLH) transcription factor that homodimerizes through leucine repeat elements and binds CAGCTG E-box motifs to activate or repress a broad repertoire of target gene promoters and enhancers, thereby regulating cell proliferation, differentiation, immune signaling, and fibrosis (PMID:2123466, PMID:2833704). TFAP4 recruits HDAC1 and additional chromatin-modifying complexes to repress transcription at specific loci, including the HIV-1 LTR and the HDM2-P2 promoter, while functioning as a transcriptional activator at numerous other targets including DVL1, LEF1, STING, IGF2BP1, DLGAP5, OX40, Itga11, and Piezo2 (PMID:16540471, PMID:19505873, PMID:30026867, PMID:39827671, PMID:36074102). During G2 phase, TFAP4 is degraded by SCF-βTrCP-mediated, phosphorylation-dependent ubiquitination; failure to degrade TFAP4 causes chromosome missegregation and multipolar spindles, establishing a cell-cycle-coupled mechanism that ensures mitotic fidelity (PMID:24500709). As a downstream effector of c-MYC, TFAP4 restricts self-renewal in proliferating B cells by activating differentiation regulators such as Spi1, SpiB, and Pax5, and its loss accelerates MYC-driven lymphomagenesis (PMID:34283887).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1988 High

    The identity and basic function of AP-4 were unknown; purification and in vitro transcription showed it is an enhancer-binding factor that activates SV40 late transcription, establishing it as a sequence-specific transcriptional activator.

    Evidence In vitro transcription assay with purified AP-4 protein on SV40 templates

    PMID:2833704

    Open questions at the time
    • No DNA-binding motif defined
    • No structural information on protein domains
    • In vivo relevance not tested
  2. 1990 High

    The structural basis for TFAP4 DNA binding and dimerization was unknown; cloning and mutagenesis revealed a bHLH protein with two additional leucine repeat elements that enforce homodimerization and restrict heterodimer formation, binding the symmetric CAGCTG E-box.

    Evidence Molecular cloning, deletion/point mutagenesis, and DNA-binding/dimerization assays

    PMID:2123466

    Open questions at the time
    • No crystal structure of HLH+LR domains
    • Functional consequences of homodimerization specificity unknown
    • No in vivo target genes identified
  3. 1994 Medium

    Whether TFAP4 participates in viral gene regulation beyond SV40 was unclear; antisense knockdown showed AP-4 is required for BLV Tax transactivation through binding CAGCTG sites in the BLV LTR, broadening its role to retroviral transcription.

    Evidence Gel retardation assay and antisense RNA knockdown with in vivo reporter assay in BLV system

    PMID:7800474

    Open questions at the time
    • Mechanism of Tax–AP-4 cooperation not defined at protein level
    • No chromatin-level evidence
  4. 2006 High

    The mechanism by which TFAP4 represses transcription was unknown; HDAC1 co-immunoprecipitation and ChIP on the HIV-1 LTR showed TFAP4 recruits HDAC1 and masks TBP binding to enforce latency, establishing a dual repressive mechanism.

    Evidence Co-IP, in vitro binding, ChIP, siRNA knockdown, and luciferase reporter in latently HIV-1-infected cells

    PMID:16540471

    Open questions at the time
    • Whether HDAC1 recruitment is a general TFAP4 repression mechanism or LTR-specific
    • No structural model of TFAP4–HDAC1 interface
  5. 2009 High

    The composition of TFAP4 repressive complexes was poorly defined; quantitative proteomics at the HDM2-P2 promoter revealed TFAP4 forms a multisubunit complex with HDAC1, CTCF, SP1, histone methyltransferases, and SWI/SNF components, indicating it operates within a broader chromatin-remodeling assemblage.

    Evidence DNA-affinity purification with cICAT/iTRAQ quantitative mass spectrometry, co-IP, and truncation mutagenesis

    PMID:19505873

    Open questions at the time
    • Stoichiometry and stability of the complex not determined
    • Whether this complex composition is promoter-specific
  6. 2014 High

    How TFAP4 protein levels are controlled during the cell cycle was unknown; biochemical and mutagenesis experiments showed SCF-βTrCP ubiquitinates TFAP4 in a phosphorylation-dependent manner during G2, and a non-degradable mutant causes mitotic defects, linking TFAP4 turnover to mitotic fidelity.

    Evidence Degradation assays, degron mutagenesis, cell cycle synchronization, mass spectrometry for phosphorylation, immunofluorescence for mitotic phenotypes

    PMID:24500709

    Open questions at the time
    • Kinase responsible for degron phosphorylation not identified
    • Whether TFAP4 re-accumulation in G1 is transcriptionally or translationally regulated
  7. 2018 Medium

    Whether TFAP4 has pathway-level transcriptional outputs in cancer was unclear; ChIP-qPCR and reporter assays demonstrated direct binding and activation of DVL1 and LEF1 promoters, establishing TFAP4 as an activator of Wnt/β-catenin signaling in hepatocellular carcinoma.

    Evidence Luciferase reporter, ChIP-qPCR, overexpression/knockdown in HCC cell lines

    PMID:30026867

    Open questions at the time
    • Genome-wide set of Wnt pathway targets not defined
    • Contribution relative to other E-box factors unknown
  8. 2021 High

    The in vivo role of TFAP4 downstream of MYC in normal and malignant hematopoiesis was unresolved; CRISPR deletion in Eμ-MYC HSPCs with transplantation showed TFAP4 restricts B-cell self-renewal and activates differentiation regulators (Spi1, SpiB, Pax5), and its loss accelerates lymphomagenesis.

    Evidence CRISPR KO in primary murine hematopoietic cells, in vivo transplantation, transcriptome profiling

    PMID:34283887

    Open questions at the time
    • Direct ChIP-seq for TFAP4 at differentiation gene loci not reported
    • Whether TFAP4 tumor-suppressive function extends beyond MYC-driven B-cell lymphoma
  9. 2022 Medium

    The expanding target gene network of TFAP4 in cancer raised questions about downstream effector mechanisms; ChIP and reporter assays showed TFAP4 directly activates IGF2BP1, which stabilizes TK1 mRNA via m6A, connecting TFAP4 to epitranscriptomic regulation of proliferation.

    Evidence ChIP, luciferase reporter, m6A detection, knockdown/overexpression, in vivo xenograft in NSCLC

    PMID:36074102

    Open questions at the time
    • Genome-wide TFAP4 ChIP-seq in NSCLC not performed
    • Whether m6A-dependent mRNA stabilization is a general downstream axis
  10. 2024 Medium

    TFAP4 protein stability regulation beyond SCF-βTrCP was unknown; co-IP and ubiquitination assays showed USP15 deubiquitinates TFAP4 to enhance its stability, and stabilized TFAP4 activates PCGF1 to promote colorectal cancer metastasis, revealing a reciprocal TFAP4–USP15 regulatory circuit.

    Evidence Co-IP, dual luciferase, ChIP, oligonucleotide pull-down, in vivo liver metastasis model (CRC); complementary study showing TFAP4 activates USP15 transcription in RCC

    PMID:38801926 PMID:38847328

    Open questions at the time
    • Whether the USP15–TFAP4 reciprocal axis operates in normal tissues
    • Relative contribution of SCF-βTrCP vs USP15 to steady-state TFAP4 levels
  11. 2025 Medium

    The breadth of TFAP4 transcriptional targets in fibrosis and immune signaling was emerging; multiple studies confirmed direct promoter activation of STING, Itga11, Piezo2, and DLGAP5, linking TFAP4 to innate immune signaling, mechanotransduction in cardiac fibrosis, and JAK2/STAT3 activation.

    Evidence ChIP, luciferase reporter, in vivo AAV8 overexpression, STING-KO epistasis, post-MI mouse models, xenograft with macrophage co-culture

    PMID:39827671 PMID:40612272 PMID:40962169

    Open questions at the time
    • No genome-wide ChIP-seq defining complete TFAP4 regulon in any fibrosis model
    • Selectivity mechanism for activator vs repressor function at different promoters unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the kinase(s) that phosphorylate the TFAP4 degron for SCF-βTrCP recognition, the structural basis for how TFAP4 switches between activator and repressor modes, the comprehensive genome-wide direct target repertoire (no TFAP4 ChIP-seq in human cells has been reported), and the physiological roles of TFAP4 in normal development beyond hematopoiesis and Drosophila tracheal branching.
  • Degron kinase identity unknown
  • No crystal or cryo-EM structure of TFAP4 homodimer on DNA
  • No comprehensive human TFAP4 ChIP-seq dataset
  • Conditional knockout phenotypes in mammalian tissues beyond hematopoietic and myeloid lineages not reported

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 12 GO:0003677 DNA binding 11
Localization
GO:0005634 nucleus 5
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-4839726 Chromatin organization 2 R-HSA-1640170 Cell Cycle 1
Partners
BTRCCTCFHDAC1SP1USP15

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 AP-4 (TFAP4) was isolated as an enhancer-binding factor that recognizes a motif in the SV40 A-domain and activates SV40 late transcription in vitro; this stimulation is augmented by AP-1 binding to adjacent sequences, demonstrating coordinate action of the two factors for transcriptional enhancement. In vitro transcription assay with purified AP-4 protein Nature High 2833704
1990 Human AP-4 (TFAP4) is a helix-loop-helix (HLH) protein that binds the symmetrical DNA sequence CAGCTG; it contains an HLH motif plus two additional leucine repeat elements (LR1 and LR2) that promote homodimerization and restrict heterodimer formation with other HLH proteins such as E12. The LR1/LR2 domains are required for solution-phase dimerization, while the HLH-basic region is sufficient for DNA binding. Molecular cloning, deletion/point mutagenesis, DNA-binding and dimerization assays Genes & development High 2123466
2006 TFAP4 represses HIV-1 LTR transcription by recruiting histone deacetylase 1 (HDAC1) to the LTR promoter and by masking TATA-binding protein (TBP) binding to the TATA box; TFAP4 and HDAC1 are present on the LTR in latently infected cells and dissociate upon TNF-α-induced reactivation. Co-immunoprecipitation, in vitro binding assay, chromatin immunoprecipitation (ChIP), siRNA knockdown, luciferase reporter assay The Journal of biological chemistry High 16540471
2009 TFAP4 binds an E-box in the HDM2-P2 promoter via its C-terminal Gln/Pro-rich domain and represses HDM2 transcription in a p53-independent manner; AP-4 forms a complex containing HDAC1, CTCF, SP1, histone methyltransferases, and SWI/SNF components at the HDM2-P2 promoter. Luciferase reporter assay, AP-4 truncation mutants, DNA-affinity purification followed by quantitative proteomics (cICAT and iTRAQ), co-immunoprecipitation Molecular & cellular proteomics High 19505873
2014 During G2 phase of the cell cycle, TFAP4 is targeted for proteasome-dependent degradation by the SCF-βTrCP ubiquitin ligase, requiring phosphorylation of TFAP4 on a conserved degron; expression of a stable TFAP4 mutant unable to interact with βTrCP causes chromosome missegregation, multipolar spindles, and DNA damage response activation. Biochemical degradation assays, site-directed mutagenesis of degron, cell cycle analysis, immunofluorescence for mitotic defects, mass spectrometry The Journal of biological chemistry High 24500709
2018 TFAP4 activates Wnt/β-catenin signaling in hepatocellular carcinoma by directly binding to the promoters of DVL1 and LEF1, as demonstrated by luciferase reporter and ChIP-qPCR assays. Luciferase reporter assay, ChIP-qPCR, overexpression/knockdown functional assays Theranostics Medium 30026867
2001 TFAP4 acts as a transcriptional ligand for immunoglobulin-κ promoter E-box elements (5′-CAGCTG-3′) and does not act as a transactivator at these sites, distinguishing it from E47. Electrophoretic mobility shift assay (EMSA) with nuclear extracts from human and murine B-cell lines The Biochemical journal Medium 11171123
1994 AP-4 participates in BLV Tax trans-activation by binding a CAGCTG AP-4 site in the 21-bp repeats of the BLV LTR; antisense AP-4 RNA strongly reduces Tax activation, indicating AP-4 is required for this viral trans-activation. Gel retardation assay, in vivo reporter assay, antisense RNA knockdown Nucleic acids research Medium 7800474
1998 AP-4 binds E-box (CACCTG) motifs in a distal regulatory region of the IGFBP-2 gene and activates IGFBP-2 promoter activity 16-fold when co-transfected with an AP-4 expression vector; stimulation is abolished by mutation of both bHLH motifs. EMSA, Southwestern blot, co-transfection luciferase reporter assay with AP-4 expression vector Endocrine Medium 9741833
2011 In IGF-1-stimulated breast cancer cells, JNK activation induces SHP1 expression through binding of TFAP4 and RFX-1 transcription factors to the epithelial tissue-specific SHP1 promoter. Promoter reporter assay, transcription factor binding assay, JNK inhibition experiments Molecular cancer research Low 21719561
2021 c-MYC suppresses the stemness of developing B cells and counteracts oncogenesis by inducing TFAP4, which restricts self-renewal of proliferating B cells; CRISPR deletion of TFAP4 in Eµ-MYC hematopoietic stem and progenitor cells accelerates c-MYC-driven lymphoma development and reduces expression of B cell differentiation regulators Spi1, SpiB, and Pax5 that are direct target genes of TFAP4. CRISPR knockout in primary hematopoietic cells with in vivo transplantation, transcriptional profiling, genetic epistasis Blood High 34283887
2015 In Drosophila, Cropped (the AP-4 ortholog) is required for tracheal terminal cell branching and is controlled by dMyc; ectopic dMyc increases Cropped protein levels and cellular branching, placing AP-4 downstream of Myc in a branching morphogenesis pathway. Genetic overexpression and loss-of-function in Drosophila tracheal cells, cell counting, protein level analysis BMC developmental biology Medium 25888431
2019 TFAP4 directly binds to the promoter of OX40 (acting as its transcription factor) and promotes OX40 expression, thereby accelerating double-negative T cell (DNT) differentiation; myeloid-specific TFAP4 knockout reduced DNTs in liver tissue and delayed liver fibrosis progression. Luciferase reporter assay, ChIP, overexpression and myeloid-specific knockout mouse model International immunopharmacology Medium 37060810
2022 TFAP4 transcriptionally activates IGF2BP1 by binding its promoter; IGF2BP1 then stabilizes TK1 mRNA via m6A modification to promote NSCLC cell proliferation, migration, and invasion. ChIP assay, luciferase reporter assay, m6A modification detection, knockdown/overexpression, in vivo xenograft Molecular cancer research Medium 36074102
2024 TFAP4 transcriptionally activates the USP15 promoter (confirmed by ChIP and pull-down assay); USP15 in turn deubiquitinates and stabilizes SHC1 protein, promoting renal cell carcinoma malignancy. ChIP assay, oligonucleotide pull-down assay, co-immunoprecipitation, ubiquitination assay, in vivo xenograft Cancer science Medium 38847328
2024 USP15 deubiquitinates TFAP4 and enhances its protein stability; stabilized TFAP4 transcriptionally activates PCGF1 to promote colorectal cancer metastasis and stemness. Co-immunoprecipitation, dual luciferase reporter assay, oligonucleotide pull-down, ChIP assay, in vivo liver metastasis model Biochemical pharmacology Medium 38801926
2019 TFAP4 binds the rs1800734 region of the MLH1 promoter (confirmed by allele-specific binding assay), but binding is much weaker to the cancer risk allele than the protective allele; TFAP4 binding is absent when promoter methylation is present, suggesting TFAP4 shields the protective allele from BRAF-induced methylation. Allele-specific TFAP4 binding assay, methylation analysis, re-expression after methylation inhibitor treatment Scientific reports Medium 31530880
2025 TFAP4 directly activates expression of mechanosensors Itga11 and Piezo2 (confirmed by ChIP/luciferase), promoting cardiac fibroblast activation, ECM deposition, and myofibroblast differentiation; silencing Itga11 and Piezo2 reverses TFAP4's pro-fibrotic effects. ChIP assay, luciferase reporter assay, overexpression/knockdown, in vivo mouse post-MI model Cell insight Medium 40612272
2025 TFAP4 transcriptionally activates the DLGAP5 promoter (confirmed by ChIP and luciferase assay); the TFAP4/DLGAP5 axis activates JAK2/STAT3 signaling in prostate cancer cells to promote tumor progression and macrophage M2 polarization. ChIP assay, luciferase reporter assay, knockdown/overexpression, co-culture macrophage polarization assay, in vivo xenograft Experimental cell research Medium 40962169
2025 TFAP4 binds the STING promoter and transcriptionally activates STING expression (shown by luciferase reporter gene experiment), thereby promoting STING signaling pathway activation and progression of liver fibrosis. Luciferase reporter assay, AAV8-TFAP4 overexpression in mice, STING-KO mouse epistasis International immunopharmacology Medium 39827671
2018 TFAP4 directly binds E-box motifs in the TRERNA1 promoter and transcriptionally regulates TRERNA1 long non-coding RNA expression in gastric cancer cells (confirmed by dual luciferase reporter and ChIP assay); TRERNA1 promotes gastric cancer cell migration and invasion. Dual luciferase reporter assay, ChIP, knockdown/overexpression Oncology reports Medium 29845218
2025 TFAP4 transcriptionally activates FOXK1 expression in prostate cancer; FOXK1 overexpression reverses the effects of TFAP4 knockdown on cell viability, migration, and invasion. RT-qPCR, Western blot, rescue overexpression experiment, CCK-8, Transwell assays Experimental and therapeutic medicine Low 34630654
2025 In T-ALL, TFAP4 binds an enhancer element to fine-tune Galectin-9 expression (identified by genome-wide CRISPR screen and transcription factor binding assay), while IRF1 binds the promoter as the primary driver. Genome-wide CRISPR screen, transcription factor binding assay, enhancer mapping, chromatin accessibility analysis Science advances Medium 40106574
2024 TFAP4 transcriptionally activates BPTF expression and promotes EMT through activating the PI3K/AKT signaling pathway in neuroblastoma, with BPTF acting as the downstream effector. Western blot, knockdown/overexpression, functional assays; upstream regulatory relationship inferred from protein co-expression and inhibitor studies Biological procedures online Low 37170211
2024 TFAP4 is required for differentiation and fusion of bovine satellite cells into myofibers; active enhancers in differentiating satellite cells are enriched for TFAP4 binding sites, and TFAP4 knockdown or overexpression experimentally alters differentiation. ChIP-seq for histone modifications, TFAP4 knockdown and overexpression in bovine satellite cells BMC genomics Medium 38475725

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1988 Enhancer binding factors AP-4 and AP-1 act in concert to activate SV40 late transcription in vitro. Nature 307 2833704
1990 Transcription factor AP-4 contains multiple dimerization domains that regulate dimer specificity. Genes & development 304 2123466
1999 AP-4, a novel protein complex related to clathrin adaptors. The Journal of biological chemistry 234 10066790
2010 Sorting of the Alzheimer's disease amyloid precursor protein mediated by the AP-4 complex. Developmental cell 215 20230749
1990 Pan: a transcriptional regulator that binds chymotrypsin, insulin, and AP-4 enhancer motifs. Genes & development 180 2200736
2002 AP-4 binds basolateral signals and participates in basolateral sorting in epithelial MDCK cells. Nature cell biology 161 11802162
2010 Adaptor protein complex-4 (AP-4) deficiency causes a novel autosomal recessive cerebral palsy syndrome with microcephaly and intellectual disability. Journal of medical genetics 140 20972249
2017 AP-4 mediates export of ATG9A from the trans-Golgi network to promote autophagosome formation. Proceedings of the National Academy of Sciences of the United States of America 139 29180427
2006 Transcriptional repression of human immunodeficiency virus type 1 by AP-4. The Journal of biological chemistry 130 16540471
2018 AP-4 vesicles contribute to spatial control of autophagy via RUSC-dependent peripheral delivery of ATG9A. Nature communications 127 30262884
2008 Accumulation of AMPA receptors in autophagosomes in neuronal axons lacking adaptor protein AP-4. Neuron 125 18341993
2012 Adaptor protein complexes AP-4 and AP-5: new players in endosomal trafficking and progressive spastic paraplegia. Traffic (Copenhagen, Denmark) 116 23167973
2001 Signal-binding specificity of the mu4 subunit of the adaptor protein complex AP-4. The Journal of biological chemistry 112 11139587
2018 Altered distribution of ATG9A and accumulation of axonal aggregates in neurons from a mouse model of AP-4 deficiency syndrome. PLoS genetics 95 29698489
2001 Functional and physical interactions of the adaptor protein complex AP-4 with ADP-ribosylation factors (ARFs). The EMBO journal 95 11707398
2018 Transcription factor AP-4 promotes tumorigenic capability and activates the Wnt/β-catenin pathway in hepatocellular carcinoma. Theranostics 85 30026867
2015 The Adaptor Complex AP-4 Regulates Vacuolar Protein Sorting at the trans-Golgi Network by Interacting with VACUOLAR SORTING RECEPTOR1. Plant physiology 72 26546666
2019 Axonal autophagosome maturation defect through failure of ATG9A sorting underpins pathology in AP-4 deficiency syndrome. Autophagy 69 31142229
2003 Adaptor protein complex-4 (AP-4) is expressed in the central nervous system neurons and interacts with glutamate receptor delta2. Molecular and cellular neurosciences 53 14572453
2014 Recessive loss-of-function mutations in AP4S1 cause mild fever-sensitive seizures, developmental delay and spastic paraplegia through loss of AP-4 complex assembly. Human molecular genetics 49 25552650
2014 An AP4B1 frameshift mutation in siblings with intellectual disability and spastic tetraplegia further delineates the AP-4 deficiency syndrome. European journal of human genetics : EJHG 44 24781758
2022 AP-4-mediated axonal transport controls endocannabinoid production in neurons. Nature communications 41 35217685
2019 TFAP4 Promotes Hepatocellular Carcinoma Invasion and Metastasis via Activating the PI3K/AKT Signaling Pathway. Disease markers 34 31281549
2019 MicroRNA-608 Promotes Apoptosis in Non-Small Cell Lung Cancer Cells Treated With Doxorubicin Through the Inhibition of TFAP4. Frontiers in genetics 33 31552102
2014 Wnt/β-catenin signaling regulates Helicoverpa armigera pupal development by up-regulating c-Myc and AP-4. Insect biochemistry and molecular biology 33 25038464
2020 Re-evaluation of Diadenosine Tetraphosphate (Ap4A) From a Stress Metabolite to Bona Fide Secondary Messenger. Frontiers in molecular biosciences 32 33282915
2020 Cucurbitacin E Chemosensitizes Colorectal Cancer Cells via Mitigating TFAP4/Wnt/β-Catenin Signaling. Journal of agricultural and food chemistry 31 33205649
2012 Down-regulation of AP-4 inhibits proliferation, induces cell cycle arrest and promotes apoptosis in human gastric cancer cells. PloS one 30 22615908
2002 The structure of Ap(4)A hydrolase complexed with ATP-MgF(x) reveals the basis of substrate binding. Structure (London, England : 1993) 30 11839306
2011 Breast cancer cells proliferation is regulated by tyrosine phosphatase SHP1 through c-jun N-terminal kinase and cooperative induction of RFX-1 and AP-4 transcription factors. Molecular cancer research : MCR 29 21719561
2020 The FTS-Hook-FHIP (FHF) complex interacts with AP-4 to mediate perinuclear distribution of AP-4 and its cargo ATG9A. Molecular biology of the cell 27 32073997
2018 MicroRNA-302c represses epithelial-mesenchymal transition and metastasis by targeting transcription factor AP-4 in colorectal cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 27 29906744
2014 A novel AP4M1 mutation in autosomal recessive cerebral palsy syndrome and clinical expansion of AP-4 deficiency. BMC medical genetics 27 25496299
2005 The adaptor protein AP-4 as a component of the clathrin coat machinery: a morphological study. The Biochemical journal 27 15377281
1988 Specific phosphorylase from Euglena gracilis splits diadenosine 5',5'''-P(1),P(4)-tetraphosphate (Ap(4)A) and diadenosine 5',5'''-P(1),P(3)-triphosphate (Ap(3)A). The International journal of biochemistry 25 21137581
2014 Proteasome-dependent degradation of transcription factor activating enhancer-binding protein 4 (TFAP4) controls mitotic division. The Journal of biological chemistry 24 24500709
2001 Transcription factor AP-4 is a ligand for immunoglobulin-kappa promoter E-box elements. The Biochemical journal 24 11171123
1994 Transcription factor AP-4 participates in activation of bovine leukemia virus long terminal repeat by p34 Tax. Nucleic acids research 24 7800474
2015 Bivalent Motif-Ear Interactions Mediate the Association of the Accessory Protein Tepsin with the AP-4 Adaptor Complex. The Journal of biological chemistry 22 26542808
2022 AP-4 regulates neuronal lysosome composition, function, and transport via regulating export of critical lysosome receptor proteins at the trans-Golgi network. Molecular biology of the cell 21 35976706
2020 An integrated pan-cancer analysis of TFAP4 aberrations and the potential clinical implications for cancer immunity. Journal of cellular and molecular medicine 21 33373169
2009 Complementary quantitative proteomics reveals that transcription factor AP-4 mediates E-box-dependent complex formation for transcriptional repression of HDM2. Molecular & cellular proteomics : MCP 21 19505873
2019 Second messenger Ap4A polymerizes target protein HINT1 to transduce signals in FcεRI-activated mast cells. Nature communications 20 31604935
1998 A distal regulatory region of the insulin-like growth factor binding protein-2 (IGFBP-2) gene interacts with the basic helix-loop-helix transcription factor, AP-4. Endocrine 20 9741833
2022 Cucurbitacin E Triggers Cellular Senescence in Colon Cancer Cells via Regulating the miR-371b-5p/TFAP4 Signaling Pathway. Journal of agricultural and food chemistry 19 35192356
2024 High-content screening identifies a small molecule that restores AP-4-dependent protein trafficking in neuronal models of AP-4-associated hereditary spastic paraplegia. Nature communications 18 38233389
2022 TFAP4 Activates IGF2BP1 and Promotes Progression of Non-Small Cell Lung Cancer by Stabilizing TK1 Expression through m6A Modification. Molecular cancer research : MCR 18 36074102
2020 Transcription factor AP-4 (TFAP4)-upstream ORF coding 66 aa inhibits the malignant behaviors of glioma cells by suppressing the TFAP4/long noncoding RNA 00520/microRNA-520f-3p feedback loop. Cancer science 18 31943575
2018 Elevated TFAP4 regulates lncRNA TRERNA1 to promote cell migration and invasion in gastric cancer. Oncology reports 18 29845218
2011 Importin beta plays an essential role in the regulation of the LysRS-Ap(4)A pathway in immunologically activated mast cells. Molecular and cellular biology 17 21402779
2020 The role of AP-4 in cargo export from the trans-Golgi network and hereditary spastic paraplegia. Biochemical Society transactions 16 33084855
1994 Production of a thermophilic, extracellular alkaline protease by Bacillus stearothermophilus AP-4. World journal of microbiology & biotechnology 16 24420882
2009 Polarized sorting of AMPA receptors to the somatodendritic domain is regulated by adaptor protein AP-4. Neuroscience research 15 19481121
2023 Diadenosine Tetraphosphate (Ap4 A) Serves as a 5' RNA Cap in Mammalian Cells. Angewandte Chemie (International ed. in English) 14 37934413
2011 The epsilon hinge-ear region regulates membrane localization of the AP-4 complex. Traffic (Copenhagen, Denmark) 14 21810154
2018 A novel homozygous AP4B1 mutation in two brothers with AP-4 deficiency syndrome and ocular anomalies. American journal of medical genetics. Part A 13 29430868
2015 Cropped, Drosophila transcription factor AP-4, controls tracheal terminal branching and cell growth. BMC developmental biology 13 25888431
2011 Phospholipase C/Protein Kinase C pathway is essential for corneal re-epithelialization induced by Ap(4)A. Current eye research 13 21988553
2022 The adaptor protein chaperone AAGAB stabilizes AP-4 complex subunits. Molecular biology of the cell 11 35976721
2016 Diadenosine tetraphosphate (Ap4A) inhibits ATP-induced excitotoxicity: a neuroprotective strategy for traumatic spinal cord injury treatment. Purinergic signalling 11 27761681
2021 Unexpected suppression of tumorigenesis by c-MYC via TFAP4-dependent restriction of stemness in B lymphocytes. Blood 10 34283887
2021 TFAP4 promotes the growth of prostate cancer cells by upregulating FOXK1. Experimental and therapeutic medicine 10 34630654
2019 The polymorphic variant rs1800734 influences methylation acquisition and allele-specific TFAP4 binding in the MLH1 promoter leading to differential mRNA expression. Scientific reports 10 31530880
2021 MicroRNA-124 suppresses the invasion and proliferation of breast cancer cells by targeting TFAP4. Oncology letters 9 33717268
2008 AP-4: autophagy-four mislocalized proteins in axons. Autophagy 9 18654090
2000 Selective degradation of 2'-adenylated diadenosine tri- and tetraphosphates, Ap(3)A and Ap(4)A, by two specific human dinucleoside polyphosphate hydrolases. Archives of biochemistry and biophysics 9 10620341
2024 The Reelin receptor ApoER2 is a cargo for the adaptor protein complex AP-4: Implications for Hereditary Spastic Paraplegia. Progress in neurobiology 8 38281682
2021 Silencing of the Long Non-Coding RNA TTN-AS1 Attenuates the Malignant Progression of Osteosarcoma Cells by Regulating the miR-16-1-3p/TFAP4 Axis. Frontiers in oncology 8 34141611
2024 Ubiquitin-specific peptidase 15 regulates the TFAP4/PCGF1 axis facilitating liver metastasis of colorectal cancer and cell stemness. Biochemical pharmacology 7 38801926
2024 USP15, activated by TFAP4 transcriptionally, stabilizes SHC1 via deubiquitination and deteriorates renal cell carcinoma. Cancer science 7 38847328
2023 Downregulation of miR-144 blocked the proliferation and invasion of nerve cells in Hirschsprung disease by regulating Transcription Factor AP 4 (TFAP4). Pediatric surgery international 7 37610449
2022 Inhibitory effect of CC chemokine ligand 23 (CCL23)/ transcription factor activating enhancer binding protein 4 (TFAP4) on cell proliferation, invasion and angiogenesis in hepatocellular carcinoma. Bioengineered 7 35001801
2019 Ap4A Regulates Directional Mobility and Antigen Presentation in Dendritic Cells. iScience 6 31254530
2025 TFAP4 regulates the progression of liver fibrosis through the STING signaling pathway. International immunopharmacology 5 39827671
2023 Deletion of the transcriptional regulator TFAP4 accelerates c-MYC-driven lymphomagenesis. Cell death and differentiation 5 36894688
2023 TFAP4 promotes the progression of liver fibrosis through regulating double-negative T cell differentiation via OX40. International immunopharmacology 5 37060810
2024 Chromatin profiling reveals TFAP4 as a critical transcriptional regulator of bovine satellite cell differentiation. BMC genomics 4 38475725
2024 Rapid Vacuolar Sorting of the Borate Transporter BOR1 Requires the Adaptor Protein Complex AP-4 in Arabidopsis. Plant & cell physiology 4 39215599
2023 BPTF in bone marrow provides a potential progression biomarker regulated by TFAP4 through the PI3K/AKT pathway in neuroblastoma. Biological procedures online 4 37170211
2022 AP-4 loss in CRISPR-edited zebrafish affects early embryo development. Advances in biological regulation 4 36642642
2016 Silencing of AP-4 inhibits proliferation, induces cell cycle arrest and promotes apoptosis in human lung cancer cells. Oncology letters 4 27313685
2001 Characterization of microsatellite markers adjacent to AP-4 on chromosome 16p13.3. Molecular and cellular probes 4 11735304
2025 TFAP4 exacerbates pathological cardiac fibrosis by modulating mechanotransduction. Cell insight 3 40612272
2024 Lymphocytic choriomeningitis arenavirus requires cellular COPI and AP-4 complexes for efficient virion production. Journal of virology 3 38334330
2021 The pLysRS-Ap4A Pathway in Mast Cells Regulates the Switch from Host Defense to a Pathological State. International journal of molecular sciences 3 34070694
2020 Comprehensive genotype-phenotype correlation in AP-4 deficiency syndrome; Adding data from a large cohort of Iranian patients. Clinical genetics 3 32895917
2017 Understanding the Presence and Roles of Ap4A (Diadenosine Tetraphosphate) in the Eye. Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics 3 28414592
1995 AP-4- and AP-5-like proteins from mouse L cells are trans-activators and bind to the GT-II region of SV40 early TRE in a mutually exclusive manner. Gene 3 7557429
2018 Increased Ap4A levels and ecto-nucleotidase activity in glaucomatous mice retina. Purinergic signalling 2 29948577
2025 TFAP4 Regulation of MCM5 Activates the PI3K/AKT Pathway to Promote Invasion and Metastasis of Gastric Cancer. Digestive diseases and sciences 1 39971831
2025 Genome-wide CRISPR screen identifies IRF1 and TFAP4 as transcriptional regulators of Galectin-9 in T cell acute lymphoblastic leukemia. Science advances 1 40106574
2025 The AP-4 accessory protein tepsin exhibits multivalent binding to LC3B. Advances in biological regulation 1 41198464
2024 circ_0006988 promotes gastric cancer cell proliferation, migration and invasion through miRNA-92a-2-5p/TFAP4 axis. Epigenomics 1 39400106
2024 Axonal organelle buildup from loss of AP-4 complex function causes exacerbation of amyloid plaque pathology and gliosis in Alzheimer's disease mouse model. eNeuro 1 39632089
2023 High-Content Small Molecule Screen Identifies a Novel Compound That Restores AP-4-Dependent Protein Trafficking in Neuronal Models of AP-4-Associated Hereditary Spastic Paraplegia. Research square 1 37398196
2023 The Plasma Membrane Purinoreceptor P2K1/DORN1 Is Essential in Stomatal Closure Evoked by Extracellular Diadenosine Tetraphosphate (Ap4A) in Arabidopsis thaliana. International journal of molecular sciences 1 38069010
2023 The Reelin Receptor ApoER2 is a Cargo for the Adaptor Protein Complex AP-4: Implications for Hereditary Spastic Paraplegia. bioRxiv : the preprint server for biology 1 38187774
2021 Corrigendum: MicroRNA-608 Promotes Apoptosis in Non-Small Cell Lung Cancer Cells Treated With Doxorubicin Through the Inhibition of TFAP4. Frontiers in genetics 1 33859675
2026 Structural basis for the dynamic conformations of AP-4 and its association with ARF1. Nature communications 0 41565640
2025 TFAP4/DLGAP5 promotes tumor progression and macrophage M2 polarization in prostate cancer by activating the JAK2/STAT3 signaling. Experimental cell research 0 40962169