Affinage

TFAP2B

Transcription factor AP-2-beta · UniProt Q92481

Length
460 aa
Mass
50.5 kDa
Annotated
2026-06-10
88 papers in source corpus 39 papers cited in narrative 39 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

TFAP2B (AP-2beta) is a neural-crest-expressed sequence-specific transcription factor that programs cell survival, differentiation, and lineage identity across multiple developing tissues by binding target promoters and enhancers to activate or repress transcription (PMID:9271117, PMID:7534010). It functions as a dimer whose DNA-binding basic domain and transactivation PY-motif are separable, and missense mutations that abolish DNA binding (R225C/R225S) or disrupt the PY motif (P62R) while preserving dimerization act dominant-negatively to cause Char syndrome, with intronic splicing mutations producing an alternative haploinsufficiency mechanism (PMID:10802654, PMID:11505339, PMID:15684060). Its transactivation is modulated by direct protein partners: GAS41 binds the AP-2beta C-terminus to enhance DNA binding and stimulate transcription (PMID:16698963), and AP-2beta interacts with and stabilizes p53 to potentiate p53-dependent target activation (PMID:21556774). Through direct promoter regulation of survival genes, AP-2beta sustains epithelial and neuronal lineages, exemplified by collecting-duct/distal-tubule survival whose loss produces apoptotic polycystic kidney disease (PMID:9271117) and by survival of sympathetic progenitors and noradrenergic neurons (PMID:21539825). AP-2beta specifies catecholaminergic neurotransmitter phenotypes by driving DBH, TH and PNMT expression — binding the PNMT promoter directly — to establish noradrenergic and adrenal epinephrine identity (PMID:18424435, PMID:20875861, PMID:26598443). In organ morphogenesis it directly controls Bmp2/Bmp4 to close the ductus arteriosus and pattern digits (PMID:21829553), lies downstream of PITX2 to differentiate corneal endothelium and form the trabecular meshwork via direct regulation of COL8A2 and ZP4 (PMID:26968737, PMID:30552118, PMID:32353428), and acts through a KCTD1 axis restraining beta-catenin to drive distal convoluted tubule differentiation (PMID:32553120). In the postnatal nervous system AP-2beta operates in GABAergic neurons to maintain GAD1/GAD2/Vgat expression and normal NREM/REM sleep architecture (PMID:37198238, PMID:32878901, PMID:38413970). AP-2beta also intersects Wnt signaling bidirectionally — recruiting beta-TrCP to degrade beta-catenin in cervical cancer (PMID:28277615) while activating beta-catenin in osteoblasts (PMID:37355029) — and regulates metabolic and tumor phenotypes through direct targets including leptin, COX-2, and an oncogenic role downstream of PAX3/FKHR (PMID:17525748, PMID:20065963, PMID:31113934).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1994 Low

    Establishing the gene's molecular identity: cloning showed AP-2beta is a functional transcription factor with tissue-restricted expression in developing midbrain and sensory neurons, framing it as a developmental regulator.

    Evidence Molecular cloning and in situ hybridization in murine embryos

    PMID:7534010

    Open questions at the time
    • Initial cloning report; transcriptional activity largely inferred
    • No target genes identified
    • No loss-of-function phenotype
  2. 1997 High

    The first knockout answered what AP-2beta does in vivo, revealing it programs epithelial cell survival during embryogenesis rather than acting merely as a differentiation factor.

    Evidence AP-2beta knockout mouse with kidney histology plus in vitro c-myc apoptosis suppression assay

    PMID:9271117

    Open questions at the time
    • Direct survival-gene targets (bcl-XL/bcl-w/bcl-2) not shown to be directly bound
    • Mechanism of anti-apoptotic action not resolved
  3. 2000 High

    Linking TFAP2B to human disease and defining its pathogenic mechanism: Char syndrome mutations dimerize normally but fail to bind DNA, establishing a dominant-negative mode.

    Evidence Positional candidacy plus in vitro dimerization, DNA-binding and transactivation assays

    PMID:10802654

    Open questions at the time
    • Domain-resolved structural basis of impaired binding not established
    • In vivo demonstration of dominant-negative effect absent
  4. 2001 High

    Extending the mechanism, additional mutants separated DNA-binding-domain (R225C/S) from transactivation-domain (P62R) lesions, both yielding dominant-negative effects and mapping functionally distinct protein regions.

    Evidence DNA-binding and transactivation assays of four mutants in eukaryotic cells

    PMID:11505339

    Open questions at the time
    • Genotype-phenotype correlation across organs not addressed
    • Endogenous target consequences not measured
  5. 2005 Medium

    Identifying an alternative disease mechanism: intronic mutations cause aberrant splicing and NMD-driven haploinsufficiency, showing TFAP2B disease arises by two distinct routes.

    Evidence Biochemical splicing assay in mammalian cells with linkage analysis

    PMID:15684060

    Open questions at the time
    • Single lab, two methods
    • Quantitative protein reduction in patients not measured
  6. 2006 High

    Defining a transactivation cofactor: GAS41 directly binds the AP-2beta C-terminus and enhances both its DNA binding and transcriptional output.

    Evidence Reciprocal Co-IP, GST pull-down, EMSA, reporter assay, domain mapping

    PMID:16698963

    Open questions at the time
    • In vivo relevance to specific target genes not shown
    • Generality across AP-2beta-regulated promoters unknown
  7. 2008 High

    Establishing a core developmental function: AP-2beta specifies the noradrenergic neurotransmitter phenotype, with NA deficiency causally explaining neonatal lethality.

    Evidence Knockout mouse neurochemistry, pharmacological rescue, gain-of-function in neural crest stem cells

    PMID:18424435

    Open questions at the time
    • Direct transcriptional targets driving NA phenotype not all defined
    • Specificity over other AP-2 family members partial
  8. 2010 High

    Showing direct promoter control of catecholaminergic identity: AP-2beta directly binds the PNMT promoter in vivo and is required for adrenal epinephrine and secretory vesicle maturation.

    Evidence Knockout mouse, neurochemistry, EM, in vivo ChIP of rat adrenal

    PMID:20875861

    Open questions at the time
    • Cofactor requirements at PNMT promoter unknown
    • Vesicle-formation defect mechanism not resolved
  9. 2011 High

    Resolving the Char-syndrome ductus phenotype mechanistically: Tfap2b directly regulates Bmp2/Bmp4 to drive ductus arteriosus closure and digit patterning.

    Evidence Knockout mouse, in situ hybridization, gel-shift and reporter assays

    PMID:21829553

    Open questions at the time
    • How BMP regulation closes the ductus mechanistically not detailed
    • Direct vs indirect limb effects partly inferred
  10. 2011 High

    Generalizing the survival role to the nervous system: AP-2beta (with AP-2alpha) maintains sympathetic progenitor and noradrenergic neuron survival.

    Evidence Constitutive and conditional double-knockout mice with TUNEL analysis

    PMID:21539825

    Open questions at the time
    • Pro-survival target genes not identified
    • Redundancy boundaries with AP-2alpha incompletely mapped
  11. 2020 High

    Placing AP-2beta in a defined differentiation pathway: it drives distal convoluted tubule differentiation via a KCTD1 axis that restrains beta-catenin.

    Evidence Conditional knockout mice with genetic epistasis (AP-2beta→KCTD1→beta-catenin)

    PMID:32553120

    Open questions at the time
    • Direct binding of AP-2beta to KCTD1 regulatory regions not shown
    • Relationship to earlier survival phenotype unclear
  12. 2016 High

    Defining an upstream regulator and ocular role: AP-2beta lies downstream of PITX2 and is required for corneal endothelium differentiation and angiogenic privilege.

    Evidence Conditional KO allelic series, microarray, qRT-PCR, in situ, IHC

    PMID:26968737

    Open questions at the time
    • Direct PITX2-to-Tfap2b regulatory link not biochemically resolved
    • Corneal target genes identified later
  13. 2017 High

    Linking AP-2beta to Wnt control in cancer: it binds beta-catenin, recruits beta-TrCP, and promotes its degradation to suppress Wnt targets and tumor growth.

    Evidence GST pull-down, reciprocal Co-IP, domain mapping, proteasome and TCF/LEF reporter assays, xenografts

    PMID:28277615

    Open questions at the time
    • Reconciliation with context-dependent Wnt activation elsewhere unresolved
    • Endogenous physiological setting beyond cancer cells unclear
  14. 2020 High

    Extending ocular function: AP-2beta in neural crest is required for trabecular meshwork and Schlemm's canal formation and intraocular pressure homeostasis.

    Evidence Wnt1Cre conditional KO, histology, IHC, TUNEL, fate mapping

    PMID:32353428

    Open questions at the time
    • Direct TM/SC differentiation targets not all defined
    • Cause of POM proliferation defect not resolved
  15. 2022 High

    Demonstrating enteric and pigment lineage roles: tfap2b is required for enteric neuron numbers (via ednrbb) and specifies a multipotent melanocyte stem cell population.

    Evidence CRISPR/Cas9 zebrafish, fate mapping, GI transit and neuron-count assays, in vitro splicing

    PMID:35021087 PMID:35874825

    Open questions at the time
    • Direct binding to ednrbb not shown
    • Conservation of stem-cell role in mammals untested
  16. 2023 High

    Establishing a postnatal physiological role: Tfap2b acts in GABAergic neurons to maintain GABAergic gene expression and normal NREM/REM sleep architecture.

    Evidence Vgat-Cre conditional KO, EEG/EMG, sleep deprivation, qPCR/RNA-seq

    PMID:32878901 PMID:37198238 PMID:38413970

    Open questions at the time
    • Direct GABAergic gene targets not defined by binding data
    • Developmental vs postnatal contributions only partly separated
  17. 2024 Medium

    Mapping a non-transcriptional cytoplasmic interaction: autophagy induction promotes an indirect, dynactin-dependent p150Glued-AP-2beta complex on lysosomes that speeds retrograde transport.

    Evidence Co-IP, rapamycin treatment, CLIP-170/dynactin siRNA, live-cell lysosome imaging, LAMP1 colocalization

    PMID:38758395

    Open questions at the time
    • Functional role of AP-2beta in transport vs bystander binding unclear
    • Relationship to its nuclear transcriptional function unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how AP-2beta's context-dependent and opposing activities — Wnt/beta-catenin degradation versus activation, tumor suppression versus PAX3/FKHR-driven oncogenic survival — are mechanistically specified by partner availability and cell type.
  • No unifying model linking cofactor context to activator vs repressor output
  • Genome-wide direct binding map across tissues incomplete
  • Structural basis of partner-dependent switching unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 5 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 2 GO:0005764 lysosome 1
Pathway
R-HSA-1266738 Developmental Biology 6 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-112316 Neuronal System 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-162582 Signal Transduction 2
Partners
BTRCCTNNB1DCTN1GAS41TP53

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 AP-2beta knockout mice die postnatally due to polycystic kidney disease caused by massive apoptotic death of collecting duct and distal tubular epithelia; in these mice, bcl-XL, bcl-w, and bcl-2 expression is down-regulated, and transfection of AP-2 into cell lines in vitro strongly suppresses c-myc-induced apoptosis, indicating AP-2beta programs cell survival during embryogenesis. Knockout mouse (loss-of-function), in vitro transfection assay, histological/molecular analysis of kidney development Genes & development High 9271117
2000 Missense mutations in TFAP2B cause Char syndrome; mutant TFAP2B proteins dimerize normally in vitro but show abnormal binding to TFAP2 target sequences, and dimerization of mutants with normal TFAP2B adversely affects transactivation, demonstrating a dominant-negative mechanism for disease pathogenesis. In vitro dimerization assay, DNA-binding assay, transactivation assay in eukaryotic cells, positional candidacy mapping Nature genetics High 10802654
2001 Four additional TFAP2B mutations cause Char syndrome: two basic-domain mutations (R225C, R225S) abolish DNA binding in vitro; a transactivation-domain PY-motif mutation (P62R) retains DNA binding but shows dominant-negative effects in eukaryotic cells. All four mutants demonstrate dominant-negative effects, consistently implicating this mechanism in Char syndrome etiology. In vitro DNA-binding assay, transactivation assay in eukaryotic cells, mutation analysis American journal of human genetics High 11505339
2005 Two intronic TFAP2B mutations in Char syndrome families cause aberrant splicing (demonstrated by biochemical studies in mammalian cells), producing frameshift mRNAs subject to nonsense-mediated decay, establishing haploinsufficiency as an alternative mechanism (distinct from dominant-negative) for TFAP2B-associated disease. Biochemical splicing assay in mammalian cells, sequencing, linkage analysis Proceedings of the National Academy of Sciences of the United States of America Medium 15684060
2006 GAS41 physically interacts with AP-2beta both in vivo (co-immunoprecipitation) and in vitro (GST pull-down); the two proteins co-localize in the nucleus; interaction maps to C-termini of both proteins; GAS41 stimulates AP-2beta transcriptional activity and enhances its DNA-binding activity as shown by EMSA. Co-immunoprecipitation, GST pull-down, co-localization (nuclear), EMSA, reporter transactivation assay, domain mapping Nucleic acids research High 16698963
2007 TFAP2B is a direct transcriptional target of the PAX3/FKHR fusion oncogene in alveolar rhabdomyosarcoma and mediates the anti-apoptotic (survival) function of PAX3/FKHR in these tumor cells, as validated by comparative expression profiling of PAX3/FKHR silencing in vitro and PAX3/FKHR-specific signatures in vivo. siRNA-mediated silencing, comparative expression profiling (in vitro and in vivo), functional anti-apoptosis validation Oncogene Medium 17525748
2008 AP-2beta represses D1A dopamine receptor gene transcription via a specific silencer element (D1AS1) in D1A-negative Neuro2a cells; AP-2beta binds the D1AS1 site (shown by gel supershift with anti-AP-2beta antibody); co-transfection of AP-2beta expression vector represses D1A promoter activity in a D1AS1-dependent manner; decoy oligonucleotides de-repress the promoter. Deletion CAT reporter analysis, gel-shift/supershift assay, co-transfection, decoy oligonucleotide experiment, RT-PCR Brain research. Molecular brain research Medium 10640692
1999 In the developing chick retina, AP-2beta (expressed in amacrine and horizontal cells) represses the R-FABP promoter; cotransfection of AP-2 expression vectors with a CAT reporter construct in primary retinal cultures decreased R-FABP-dependent expression; R-FABP mRNA and AP-2beta show mutually exclusive expression patterns. cDNA cloning, in situ hybridization, co-transfection reporter assay in primary retinal cultures, mutational analysis of AP-2 binding site Developmental dynamics Medium 10090146
2008 AP-2beta is required for noradrenaline (NA) neurotransmitter phenotype specification in both peripheral sympathetic ganglia and locus coeruleus; AP-2beta null mice show significantly reduced NA and dopamine beta-hydroxylase levels; pharmacological rescue with NA intermediate during pregnancy significantly rescues neonatal lethality of AP-2beta(-/-) mice, indicating NA deficiency is a main cause of lethality; forced expression of AP-2beta (but not other AP-2 factors) in neural crest stem cells favors their differentiation into NA neurons. Knockout mouse, neurochemical assay (NA/DBH measurement), pharmacological rescue experiment, forced expression in neural crest stem cells The Journal of biological chemistry High 18424435
2010 AP-2beta is required for the epinephrine neurotransmitter phenotype and maturation of adrenal chromaffin cells; AP-2beta(-/-) mice show reduced DBH and PNMT expression and >80% reduction in adrenal epinephrine; ultrastructural analysis reveals defective large secretory vesicle formation; ChIP assay of rat adrenal gland shows AP-2beta directly binds the PNMT gene upstream promoter in vivo. Knockout mouse, immunohistochemistry, neurochemical assay (EPI/catecholamine measurement), ultrastructural analysis (EM), chromatin immunoprecipitation (ChIP) Molecular and cellular neurosciences High 20875861
2011 Tfap2b is expressed throughout ductus arteriosus development; Tfap2b knockout mice fail to close the ductus arteriosus after birth; Tfap2b directly controls Bmp2 and Bmp4 promoter activity (shown by gel-shift assay and reporter assays); loss of Tfap2b alters Bmp2 and Bmp4 expression in limb buds, causing postaxial accessory digits. Knockout mouse, in situ hybridization, histological analysis, gel-shift assay, promoter-reporter transfection assay PloS one High 21829553
2011 AP-2beta and AP-2alpha are required for survival of sympathetic progenitors and differentiated noradrenergic neurons; AP-2beta knockout alone reduces sympathetic ganglion size ~40% via apoptotic death of neural crest progenitors and causes complete absence of locus coeruleus noradrenergic neurons; conditional double knockout of AP-2alpha/AP-2beta in sympathetic progenitors leads to near-complete loss of neurons postnatally. Constitutive and conditional knockout mice, histological/TUNEL analysis, conditional double KO with Cre-lox Developmental biology High 21539825
2005 AP-2beta overexpression in 3T3-L1 adipocytes causes cell enlargement, triglyceride accumulation, and enhanced glucose uptake via PLC and atypical PKCzeta/lambda (but not PI3-K) signaling; AP-2beta also activates Gab1 tyrosine phosphorylation and its association with PLCgamma; AP-2beta overexpression impairs insulin signaling; siRNA knockdown of AP-2beta inhibits glucose uptake. Overexpression and siRNA knockdown in 3T3-L1 adipocytes, pharmacological inhibitor experiments, kinase activity assays, co-immunoprecipitation Endocrinology Medium 16373417
2010 AP-2beta directly inhibits leptin expression in 3T3-L1 adipocytes by binding to the leptin promoter; overexpression decreases leptin promoter activity, mRNA, and protein secretion; knockdown increases leptin expression; EMSA and ChIP confirm specific AP-2beta binding to the leptin promoter (position +34 to +42 relative to TSS); site-directed mutagenesis of this AP-2 binding site abolishes the inhibitory effect. Overexpression, siRNA knockdown, promoter-reporter assay, EMSA, ChIP, site-directed mutagenesis International journal of obesity High 20065963
2020 AP-2beta is required for the differentiation of distal tubule precursors into early-stage distal convoluted tubules (DCTs) during nephrogenesis; its downstream target KCTD1 is essential for terminal differentiation of early DCTs into mature DCTs; KCTD1 deficiency leads to severe salt-losing tubulopathy and renal fibrosis by failing to repress beta-catenin activity; AP-2beta/KCTD1 axis links developmental pathway to maintenance of terminal differentiation. Genetic knockout (conditional), histological analysis, epistasis analysis (AP-2beta→KCTD1→beta-catenin) Developmental cell High 32553120
2016 PITX2 is required for expression of Tfap2b in neural crest cells during corneal development; AP-2beta in turn is required for differentiation of corneal endothelium (markers absent in AP-2beta null) and for establishment of angiogenic privilege (blood vessels invade corneal stroma in AP-2beta null), placing AP-2beta downstream of PITX2 in the corneal development pathway. Conditional knockout (temporal Pitx2 KO and Tfap2b allelic series), microarray, qRT-PCR, in situ hybridization, immunohistochemistry Investigative ophthalmology & visual science High 26968737
2017 TFAP2B mediates noradrenergic neuronal differentiation in neuroblastoma: re-expression of TFAP2B in IMR-32 cells induces neuronal differentiation with upregulation of DBH and TH and downregulation of MYCN and REST; shRNA-mediated knockdown of TFAP2B abrogates retinoic-acid-induced neuronal differentiation of neuroblastoma cells; TFAP2B is silenced by CpG methylation in primary neuroblastomas and demethylation restores expression. Tetracycline-inducible expression, lentiviral shRNA knockdown, microarray analysis, methylation analysis, 5-aza-2'-deoxycytidine demethylation Molecular oncology Medium 26598443
2017 AP-2beta interacts with beta-catenin both in vitro (GST pull-down) and in vivo (co-immunoprecipitation); the interaction involves the DNA-binding domain of AP-2beta and Armadillo repeats 1–9 of beta-catenin; AP-2beta recruits beta-TrCP and promotes proteasomal degradation of endogenous beta-catenin, thereby inhibiting Wnt/beta-catenin target gene expression and suppressing cervical cancer cell growth in vitro and in vivo. GST pull-down, co-immunoprecipitation, domain mapping, proteasome inhibitor assay, reporter assay (TCF/LEF), immunohistochemistry, xenograft in vivo assay Molecular carcinogenesis High 28277615
2018 TFAP2B directly binds the COX-2 promoter (confirmed by biotin-labeled promoter pulldown and luciferase reporter assays) to activate COX-2 expression; TFAP2B knockdown or overexpression modulates thyroid cancer cell proliferation, apoptosis, invasion, and migration via the COX-2 signaling pathway in vitro and in vivo. Biotin-labeled promoter pulldown, luciferase reporter assay, siRNA knockdown, overexpression, xenograft mouse model Cell death & disease Medium 31113934
2018 TFAP2B binds the promoters of COL8A2 and ZP4 genes and transcriptionally regulates their expression in human corneal endothelial cells (CECs); siRNA-mediated knockdown of TFAP2B in CECs decreases COL8A2 and ZP4 expression and suppresses cell proliferation. siRNA knockdown, reporter gene assay, biochemical (promoter binding) assay, quantitative RT-PCR, immunohistochemistry The Journal of biological chemistry Medium 30552118
2015 In the developing chick limb, AP-2beta expression downstream of FGF signals from the apical ectodermal ridge controls digit morphogenesis; ectopic expression of dominant-negative AP-2beta (equivalent to human Char syndrome mutants) causes reductions in phalange number and length; AP-2beta expression pattern correlates with digit length across amniote species. Ectopic expression of dominant-negative constructs in chick hindlimb bud, in situ hybridization, comparative expression analysis Developmental biology Medium 26277217
2017 In the developing cerebellum, Tfap2b is selectively expressed by interneurons (not Purkinje cells); in utero electroporation shows Tfap2b is necessary for interneuron specification and capable of suppressing generation of excitatory cells; Tfap2a (but not Tfap2b) can induce interneuron generation when misexpressed in ventricular neuroepithelium. In utero electroporation (gain- and loss-of-function), immunohistochemistry, genetic mouse analysis Frontiers in molecular neuroscience Medium 28912684
2011 AP-2beta interacts with p53 and stabilizes p53 protein; AP-2beta enhances p53-mediated transactivation of the alphaB-crystallin (CRYAB) gene promoter in a p53-dependent manner, as shown by luciferase reporter assay; AP-2beta alone does not activate the CRYAB promoter in the absence of p53. Luciferase reporter assay, co-immunoprecipitation (interaction with p53), protein stability assay Molecular biology reports Medium 21556774
2011 Postprandial activation of PKCmu positively regulates MCP-1 and IL-6 expression and negatively regulates adiponectin expression via AP-2beta; overexpression of PKCmu enhances the stimulatory and inhibitory effects of AP-2beta on these adipocytokines; PKCmu cannot activate a mutant MCP-1 promoter lacking the AP-2beta binding domain, placing AP-2beta downstream of PKCmu in the postprandial adipocytokine regulatory pathway. Overexpression, promoter-reporter assay, binding site mutagenesis, signaling pathway analysis in 3T3-L1 adipocytes International journal of molecular medicine Medium 21424113
2012 AP-2beta regulates apolipoprotein E (apoE) transcription in mouse primary astrocytes in response to amyloid-beta42 (Abeta42); Abeta42 increases AP-2beta nuclear levels while reducing AP-2alpha; in cells expressing AP-2 and incubated with Abeta42, the apoE promoter containing AP-2 binding sites shows enhanced activation compared to AP-2-deficient cells. Primary astrocyte culture, nuclear fractionation, promoter-reporter assay, pharmacological (beta-adrenergic receptor antagonist) experiments Brain research Low 22325097
2018 AP-2beta inhibits hepatocellular carcinoma (HCC) cell invasion and metastasis by suppressing EMT through downregulation of Slug and Snail; AP-2beta overexpression reduces HCC proliferation, migration, invasion, and metastasis in vitro and in vivo; oncogenic miR-27a inhibits AP-2beta expression by directly binding its 3' UTR, reversing the tumor-suppressive role. Overexpression and knockdown, in vitro migration/invasion assays, in vivo mouse experiments, miRNA-3'UTR binding assay Theranostics Medium 30026878
2020 AP-2beta is required for formation of the trabecular meshwork (TM) and Schlemm's canal (SC) in mouse eyes; conditional deletion of AP-2beta in neural crest cells causes defective POM proliferation in the angle region postnatally, loss of TM and SC marker expression, and elevated intraocular pressure. Conditional knockout (Wnt1Cre; Tfap2b-/lox), histology, immunohistochemistry, TUNEL assay, ultrastructural analysis, fate mapping Experimental eye research High 32353428
2022 tfap2b disruption in zebrafish (CRISPR/Cas9) leads to decreased enteric neuronal numbers and delayed gastrointestinal transit time; tfap2b crispants show decreased ednrbb mRNA, a downstream target; in vitro studies showed that a human TFAP2B deletion causes loss of exon 4 and absence of TFAP2B protein via premature stop codon. CRISPR/Cas9 zebrafish model, enteric neuron counting, GI transit assay, in vitro splicing assay, WES Frontiers in cell and developmental biology Medium 35874825
2020 Tfap2b specifies a melanocyte stem cell (McSC) population at the dorsal root ganglia in zebrafish; Tfap2b is required for McSC-dependent melanocyte regeneration (only a few late-stage embryonic melanocytes require it); fate mapping reveals tfap2b+ McSCs have multifate potential, giving rise to melanocytes, iridophores, xanthophores, and nerve-associated cells. Genetic loss-of-function, fate mapping, live imaging, clonal analysis in zebrafish Cell reports High 35021087
2023 Tfap2b acts in postnatal GABAergic neurons to regulate sleep; specific deletion of Tfap2b in GABAergic neurons (Vgat-tfap2b-/-) causes shortened NREM and REM sleep time and reduced delta and theta power under baseline conditions and during rebound sleep; GABAergic gene expression (GAD1, GAD2, Vgat) is downregulated in cortex, brainstem, and cerebellum of Tfap2b+/- mice. Conditional knockout (Vgat-Cre), EEG/EMG recording, sleep deprivation paradigm, qPCR, RNA-seq Scientific reports High 37198238
2020 Tfap2b heterozygous and intron-mutant mice show altered sleep architecture (increased wakefulness, decreased NREMS, or fragmented NREMS depending on allele); Tfap2b-LacZ expression in adult brain localizes to superior colliculus, locus coeruleus, cerebellum, and nucleus of the solitary tract; embryonic brain TFAP2B protein levels are reduced in splicing mutants. CRISPR/Cas9-generated mutant mice, EEG/EMG recording, LacZ reporter expression, western blot Genetics Medium 32878901
2024 TFAP2B in postnatal neurons is required for normal NREM sleep; nervous system-specific deletion of Tfap2b during development causes more severe sleep phenotypes than postnatal neuronal deletion, including defective light entrainment of the circadian clock and stereotypic jumping behavior, indicating TFAP2B functions at multiple stages and/or cell types. Cre-loxP conditional deletion (nervous system-specific and postnatal neuronal-specific), EEG/EMG recording Molecular brain Medium 38413970
2009 AP-2beta overexpression in HIT-T15 insulin-secreting cells inhibits glucose-induced insulin secretion; this is accompanied by decreased Kir6.2 and glucokinase expression; tolbutamide-induced but not KCl-induced secretion is also suppressed, suggesting the effect is upstream of membrane depolarization. Adenoviral overexpression, insulin secretion assay, western blot/RT-PCR for downstream targets Diabetes research and clinical practice Low 19596470
2024 TFAP2B directly binds the BNIP3 gene promoter to transcriptionally activate BNIP3 expression in neurons; TFAP2B overexpression in primary neurons reduces apoptosis and enhances pro-survival BNIP3-mediated mitophagy during oxygen-glucose deprivation/reperfusion injury; TFAP2B also reduces MCAO/R damage in vivo. Overexpression in primary neurons, RNA-seq, promoter binding validation experiments, OGD/R in vitro model, MCAO/R rat model Molecular neurobiology Low 38381297
2023 Ap-2beta activates Wnt/beta-catenin signaling in osteoblasts; Ap-2beta overexpression increases nuclear beta-catenin and Wnt target gene expression; Ap-2beta knockdown in frontal preosteoblasts reduces proliferation, increases cell death, impairs differentiation, and reduces active beta-catenin; Ap-2beta's osteogenic function cannot be rescued by pharmacological (LiCl) Wnt activation when Ap-2beta itself is absent, suggesting it acts upstream of beta-catenin. Knockdown, overexpression via lentivirus, luciferase reporter (beta-catenin/TCF/LEF), RNA-seq, pharmacological Wnt activation Developmental biology Medium 37355029
2024 TFAP2B transcriptionally regulates SIRT1 expression to inhibit NF-kappaB activation by reducing acetylation of the p65 subunit, thereby suppressing osteoclast differentiation; TFAP2B overexpression inhibits and knockdown promotes RANKL-induced osteoclast differentiation; TFAP2B and SIRT1 are down-regulated in middle ear cholesteatoma clinical samples. Overexpression, knockdown, osteoclast differentiation assay (RANKL-induced RAW264.7), western blot, immunohistochemistry, NF-kappaB reporter Biochemical and biophysical research communications Low 39946982
2024 Autophagy initiation (via mTORC1 inhibition by rapamycin) enhances p150Glued-AP-2beta complex formation in neurons and non-neuronal cells; this interaction is indirect and requires integrity of the dynactin complex; in non-neuronal cells the interaction also requires CLIP-170, active autophagy, and an intact endolysosomal system; the rapamycin-dependent p150Glued-AP-2beta interaction occurs on LAMP1-positive organelles and correlates with increased speed of retrograde lysosome transport. Co-immunoprecipitation, rapamycin treatment, siRNA knockdown of CLIP-170/dynactin subunits, live-cell imaging of lysosome transport, LAMP1 colocalization Cellular and molecular life sciences Medium 38758395
1994 AP-2beta was molecularly cloned and shown to encode a functional transcription factor; in situ hybridizations of murine embryo sections revealed tissue-specific and temporally restricted expression in the developing midbrain and in sensory neurons for taste, olfaction, and palpation. Molecular cloning, in situ hybridization Verhandlungen der Deutschen Gesellschaft fur Pathologie Low 7534010
2025 In molecular apocrine (ER-negative, AR-positive) breast cancer cells, AP-2beta occupies active enhancers co-bound by AR, GATA3, and FOXA1; genes defining molecular apocrine identity are significantly more likely to have active enhancers co-occupied by all four transcription factors; when present alone, AP-2beta is preferentially enriched at active promoters; reducing AP-2beta expression potently inhibits proliferation and viability associated with downregulation of MYC oncogene expression. ChIP-seq for AP-2beta, AR, GATA3, FOXA1, and H3K27ac; siRNA knockdown with proliferation/viability assay bioRxivpreprint Medium bio_10.1101_2025.07.05.663274

Source papers

Stage 0 corpus · 88 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Enhanced apoptotic cell death of renal epithelial cells in mice lacking transcription factor AP-2beta. Genes & development 235 9271117
2000 Mutations in TFAP2B cause Char syndrome, a familial form of patent ductus arteriosus. Nature genetics 187 10802654
2016 Melatonin inhibits AP-2β/hTERT, NF-κB/COX-2 and Akt/ERK and activates caspase/Cyto C signaling to enhance the antitumor activity of berberine in lung cancer cells. Oncotarget 94 26672764
2007 Comparative expression profiling identifies an in vivo target gene signature with TFAP2B as a mediator of the survival function of PAX3/FKHR. Oncogene 83 17525748
2006 Association study of the INPP1, 5HTT, BDNF, AP-2beta and GSK-3beta GENE variants and restrospectively scored response to lithium prophylaxis in bipolar disorder. Neuroscience letters 77 16787706
2001 Novel TFAP2B mutations that cause Char syndrome provide a genotype-phenotype correlation. American journal of human genetics 76 11505339
2005 Syndromic patent ductus arteriosus: evidence for haploinsufficient TFAP2B mutations and identification of a linked sleep disorder. Proceedings of the National Academy of Sciences of the United States of America 58 15684060
2005 Genetic variations in the gene encoding TFAP2B are associated with type 2 diabetes mellitus. Journal of human genetics 55 15940393
2011 The transcription factors AP-2β and AP-2α are required for survival of sympathetic progenitors and differentiated sympathetic neurons. Developmental biology 43 21539825
2011 A heart-hand syndrome gene: Tfap2b plays a critical role in the development and remodeling of mouse ductus arteriosus and limb patterning. PloS one 43 21829553
1999 Differential expression of AP-2alpha and AP-2beta in the developing chick retina: repression of R-FABP promoter activity by AP-2. Developmental dynamics : an official publication of the American Association of Anatomists 43 10090146
2006 GAS41 interacts with transcription factor AP-2beta and stimulates AP-2beta-mediated transactivation. Nucleic acids research 39 16698963
2000 A polymorphic region in the human transcription factor AP-2beta gene is associated with specific personality traits. Molecular psychiatry 39 10822354
2006 Genes encoding for AP-2beta and the Serotonin Transporter are associated with the Personality Character Spiritual Acceptance. Neuroscience letters 37 17123722
2011 Implications of central obesity-related variants in LYPLAL1, NRXN3, MSRA, and TFAP2B on quantitative metabolic traits in adult Danes. PloS one 35 21674055
2005 The transcription factor AP-2beta causes cell enlargement and insulin resistance in 3T3-L1 adipocytes. Endocrinology 35 16373417
2015 Transcription factor activating protein 2 beta (TFAP2B) mediates noradrenergic neuronal differentiation in neuroblastoma. Molecular oncology 34 26598443
2014 Association study of common polymorphisms in MSRA, TFAP2B, MC4R, NRXN3, PPARGC1A, TMEM18, SEC16B, HOXB5 and OLFM4 genes with obesity-related traits among Portuguese children. Journal of human genetics 34 24670271
2019 TFAP2B overexpression contributes to tumor growth and progression of thyroid cancer through the COX-2 signaling pathway. Cell death & disease 33 31113934
2017 Distinct Activities of Tfap2A and Tfap2B in the Specification of GABAergic Interneurons in the Developing Cerebellum. Frontiers in molecular neuroscience 32 28912684
2010 Polymorphisms in NRXN3, TFAP2B, MSRA, LYPLAL1, FTO and MC4R and their effect on visceral fat area in the Japanese population. Journal of human genetics 32 20703240
2000 The genotype of human transcription factor AP-2beta is associated with platelet monoamine oxidase B activity. Neuroscience letters 32 10984642
2020 AP-2β/KCTD1 Control Distal Nephron Differentiation and Protect against Renal Fibrosis. Developmental cell 31 32553120
2012 Analyses of GATA4, NKX2.5, and TFAP2B genes in subjects from southern China with sporadic congenital heart disease. Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology 31 22959235
2008 Regulation of the noradrenaline neurotransmitter phenotype by the transcription factor AP-2beta. The Journal of biological chemistry 31 18424435
2018 AP-2β inhibits hepatocellular carcinoma invasion and metastasis through Slug and Snail to suppress epithelial-mesenchymal transition. Theranostics 30 30026878
2012 TFAP2B influences the effect of dietary fat on weight loss under energy restriction. PloS one 28 22952648
2017 Targeting NF-κB/AP-2β signaling to enhance antitumor activity of cisplatin by melatonin in hepatocellular carcinoma cells. American journal of cancer research 27 28123844
2001 Levels of transcription factors AP-2alpha and AP-2beta in the brainstem are correlated to monoamine turnover in the rat forebrain. Neuroscience letters 27 11684350
2022 Tfap2b specifies an embryonic melanocyte stem cell that retains adult multifate potential. Cell reports 26 35021087
2019 Mutations in TFAP2B and previously unimplicated genes of the BMP, Wnt, and Hedgehog pathways in syndromic craniosynostosis. Proceedings of the National Academy of Sciences of the United States of America 26 31292255
2017 Lobular carcinoma in situ and invasive lobular breast cancer are characterized by enhanced expression of transcription factor AP-2β. Laboratory investigation; a journal of technical methods and pathology 26 29035379
2016 AP-2β Is a Downstream Effector of PITX2 Required to Specify Endothelium and Establish Angiogenic Privilege During Corneal Development. Investigative ophthalmology & visual science 24 26968737
2003 Transcription factor AP-2beta genotype associated with anxiety-related personality traits in women. A replication study. Neuropsychobiology 22 14673213
2021 Transcription factor AP-2beta in development, differentiation and tumorigenesis. International journal of cancer 21 33720400
2017 Transcription factor AP-2β suppresses cervical cancer cell proliferation by promoting the degradation of its interaction partner β-catenin. Molecular carcinogenesis 21 28277615
2013 TFAP2B -dietary protein and glycemic index interactions and weight maintenance after weight loss in the DiOGenes trial. Human heredity 21 24081236
2008 Novel TFAP2B mutation in nonsyndromic patent ductus arteriosus. Genetic testing 21 18752453
2009 The transcription factor TFAP2B is associated with insulin resistance and adiposity in healthy adolescents. Obesity (Silver Spring, Md.) 20 19325541
2020 Long non-coding RNA TP73-AS1 promotes TFAP2B-mediated proliferation, metastasis and invasion in retinoblastoma via decoying of miRNA-874-3p. Journal of cell communication and signaling 19 32067207
2018 Transcription factor TFAP2B up-regulates human corneal endothelial cell-specific genes during corneal development and maintenance. The Journal of biological chemistry 19 30552118
2011 Familial nonsyndromic patent ductus arteriosus caused by mutations in TFAP2B. Pediatric cardiology 19 21643846
2010 Transcription factor AP-2beta inhibits expression and secretion of leptin, an insulin-sensitizing hormone, in 3T3-L1 adipocytes. International journal of obesity (2005) 18 20065963
1999 AP-2beta represses D(1A) dopamine receptor gene transcription in neuro2a cells. Brain research. Molecular brain research 18 10640692
2023 Ap-2β regulates cranial osteogenic potential via the activation of Wnt/β-catenin signaling pathway. Developmental biology 17 37355029
2009 Relation of the expression of transcriptional factor TFAP2B to that of adipokines in subcutaneous and omental adipose tissues. Obesity (Silver Spring, Md.) 16 20019683
2012 AP-2β regulates amyloid beta-protein stimulation of apolipoprotein E transcription in astrocytes. Brain research 15 22325097
2010 Transcription factor AP-2β regulates the neurotransmitter phenotype and maturation of chromaffin cells. Molecular and cellular neurosciences 15 20875861
2003 Transcription factor AP-2beta genotype, striatal dopamine D2 receptor density and cerebrospinal fluid monoamine metabolite concentrations in humans. Journal of neural transmission (Vienna, Austria : 1996) 14 15057523
2015 AP-2β is a transcriptional regulator for determination of digit length in tetrapods. Developmental biology 12 26277217
2022 TFAP2B Haploinsufficiency Impacts Gastrointestinal Function and Leads to Pediatric Intestinal Pseudo-obstruction. Frontiers in cell and developmental biology 11 35874825
2017 TFAP2B mutation and dental anomalies. Journal of human genetics 11 28381879
2021 Anomalous incisor morphology indicates tissue-specific roles for Tfap2a and Tfap2b in tooth development. Developmental biology 10 33460639
2011 Association between neonatal temperament, SLC6A4, DRD4 and a functional polymorphism located in TFAP2B. Genes, brain, and behavior 10 21504541
2018 Tfap2b mutation in mice results in patent ductus arteriosus and renal malformation. The Journal of surgical research 9 29804851
2024 Novel Circular RNA CircUBAP2 Drives Tumor Progression by Regulating the miR-143/TFAP2B Axis in Prostate Cancer. Protein and peptide letters 8 37962045
2023 Tfap2b acts in GABAergic neurons to control sleep in mice. Scientific reports 8 37198238
2020 AP-2β is required for formation of the murine trabecular meshwork and Schlemm's canal. Experimental eye research 8 32353428
2020 Sleep Architecture in Mice Is Shaped by the Transcription Factor AP-2β. Genetics 8 32878901
2024 ATOH1, TFAP2B, and CEACAM6 as Immunohistochemical Markers to Distinguish Merkel Cell Carcinoma and Small Cell Lung Cancer. Cancers 7 38398178
2017 Generation of a new mouse model of glaucoma characterized by reduced expression of the AP-2β and AP-2δ proteins. Scientific reports 7 28894266
2016 AP-2α and AP-2β regulate dorsal interneuron specification in the spinal cord. Neuroscience 7 27984181
2008 Electrophysiological and behavioral correlates of polymorphisms in the transcription factor AP-2beta coding gene. Neuroscience letters 7 18358611
2024 Transcription Factor TFAP2B Exerts Neuroprotective Effects Targeting BNIP3-Mediated Mitophagy in Ischemia/Reperfusion Injury. Molecular neurobiology 6 38381297
2022 The regulatory role of AP-2β in monoaminergic neurotransmitter systems: insights on its signalling pathway, linked disorders and theragnostic potential. Cell & bioscience 6 36076256
2020 miR-142-5p promotes renal cell tumorigenesis by targeting TFAP2B. Oncology letters 6 33123240
2018 Conditional Deletion of AP-2α and AP-2β in the Developing Murine Retina Leads to Altered Amacrine Cell Mosaics and Disrupted Visual Function. Investigative ophthalmology & visual science 6 29715367
2024 Autophagy initiation triggers p150Glued-AP-2β interaction on the lysosomes and facilitates their transport. Cellular and molecular life sciences : CMLS 5 38758395
2021 Conditional Deletion of AP-2β in the Periocular Mesenchyme of Mice Alters Corneal Epithelial Cell Fate and Stratification. International journal of molecular sciences 5 34445433
2018 A study of familial Char syndrome involving the TFAP2B gene with a focus on facial shape characteristics. Clinical dysmorphology 5 29683802
2011 Postprandial activation of protein kinase Cµ regulates the expression of adipocytokines via the transcription factor AP-2β. International journal of molecular medicine 5 21424113
2011 AP-2β enhances p53-mediated transcription of the αB-crystallin gene through stabilizing p53. Molecular biology reports 5 21556774
2002 No association between a transcription factor Activating Protein 2beta (AP-2beta) gene variant and schizophrenia. Neuroscience letters 5 12270648
2024 AP-2α/AP-2β Transcription Factors Are Key Regulators of Epidermal Homeostasis. The Journal of investigative dermatology 4 38237728
2019 A novel missense mutation in TFAP2B associated with Char syndrome and central diabetes insipidus. American journal of medical genetics. Part A 4 31012281
2023 Generation of tamoxifen-inducible Tfap2b-CreERT2 mice using CRISPR-Cas9. Genesis (New York, N.Y. : 2000) 3 38069547
2016 Single nucleotide polymorphisms in AGTR1, TFAP2B, and TRAF1 are not associated with the incidence of patent ductus arteriosus in Japanese preterm infants. Pediatrics international : official journal of the Japan Pediatric Society 3 26615960
1994 [Molecular cloning of a new AP-2 transcription factor, AP-2beta, and its function in cell differentiation]. Verhandlungen der Deutschen Gesellschaft fur Pathologie 3 7534010
2025 TFAP2B governs the regulation of SIRT1 to inhibit osteoclast-induced bone destruction. Biochemical and biophysical research communications 2 39946982
2024 Transcriptional programs of Pitx2 and Tfap2a/Tfap2b controlling lineage specification of mandibular epithelium during tooth initiation. PLoS genetics 2 39052671
2021 Co-expression of transcription factor AP-2beta (TFAP2B) and GATA3 in human mammary epithelial cells with intense, apicobasal immunoreactivity for CK8/18. Journal of molecular histology 2 34117603
2009 Transcription factor AP-2beta inhibits glucose-induced insulin secretion in cultured insulin-secreting cell-line. Diabetes research and clinical practice 2 19596470
2023 AP-2α/AP-2β transcription factors are key regulators of epidermal homeostasis. bioRxiv : the preprint server for biology 1 38105942
2021 Deletion of transcription factor AP-2β from the developing murine trabecular meshwork region leads to progressive glaucomatous changes. Journal of neuroscience research 1 34822722
2010 Does the transcription factor AP-2beta have an impact on the genetic and early environmental influence on ethanol consumption? Journal of neural transmission (Vienna, Austria : 1996) 1 20690033
2024 Crucial role of TFAP2B in the nervous system for regulating NREM sleep. Molecular brain 0 38413970
2024 [Clinical characteristics and genetic analysis of a child with Char syndrome caused by TFAP2B gene variant]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 0 39097275
2010 [Mutation of TFAP-2B gene in patients with patent ductus arteriosus]. Zhonghua er ke za zhi = Chinese journal of pediatrics 0 21215182

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