Affinage

REPIN1

DNA-binding protein REPIN1 · UniProt Q9BWE0

Length
567 aa
Mass
63.6 kDa
Annotated
2026-06-10
100 papers in source corpus 8 papers cited in narrative 8 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

REPIN1 (RIP60) is a 15-zinc-finger nuclear DNA-binding protein originally defined by its sequence-specific recognition of ATT-rich elements at mammalian DNA replication origins, and now recognized as a regulator of lipid and glucose metabolism in metabolic tissues (PMID:2174103, PMID:24760138). The protein was purified from HeLa nuclear extract as a 60-kDa polypeptide that binds the Chinese hamster DHFR replication origin (oribeta) and co-fractionates with an ATP-dependent DNA helicase, RIP100, implicating it in initiation of chromosomal DNA synthesis (PMID:2174103). Its C2H2 zinc fingers are organized into three clusters (Z1, Z2, Z3) plus an intervening proline-rich region; the Z1 and Z2 hands independently confer specific oribeta binding while the Z2 hand together with the adjacent proline-rich region drives multimerization and formation of a twisted DNA loop, and origin binding accentuates local DNA bending (PMID:2247056, PMID:10606657). Beyond its origin-binding biochemistry, REPIN1 controls metabolic phenotypes: liver-specific deletion in mice improves whole-body insulin sensitivity and lowers hepatic triglyceride content while altering CD36, PPARγ, GLUT2, Akt phosphorylation, and lipocalin2 (PMID:24760138), and knockdown in adipocytes regulates cell size, glucose-transporter (GLUT1/GLUT4) expression, and glucose and palmitate uptake (PMID:20727851). Hepatocellular REPIN1 is required for the early lipid accumulation that supports efficient liver regeneration after partial hepatectomy via CD36 and FATP5 (PMID:30442920), and in osteoblasts it promotes iron-overload-induced apoptosis by inducing LCN2 (PMID:37749079).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 1990 High

    Established that REPIN1/RIP60 is an origin-specific DNA-binding protein physically associated with helicase activity, placing it at the initiation of chromosomal replication.

    Evidence 9,000-fold protein purification from HeLa nuclear extract with protein-DNA cross-linking, oligonucleotide displacement, and ATP-labeling of a co-purifying 100-kDa helicase

    PMID:2174103

    Open questions at the time
    • Whether RIP60 and the RIP100 helicase form a stable complex in vivo was not established
    • No demonstration that RIP60 binding is required for origin firing in cells
  2. 1990 High

    Resolved how REPIN1 engages origin DNA structurally, showing it enhances bending at an ATT-rich element of the DHFR oribeta.

    Evidence Circular permutation and gel mobility shift assays with purified RIP60 on circularly permuted bent DNA fragments

    PMID:2247056

    Open questions at the time
    • Functional consequence of induced bending for replication initiation not tested
    • Did not define which zinc fingers mediate bending
  3. 2000 High

    Defined the domain architecture and a DNA-looping mechanism, showing distinct zinc-finger clusters mediate specific binding versus multimerization.

    Evidence One-hybrid cloning, DNase I footprinting, EMSA, ligation enhancement, and atomic force microscopy visualizing a ~720 bp DNA loop; plasmid replication assay

    PMID:10606657

    Open questions at the time
    • Only weak replication enhancer activity observed, leaving the replication role unresolved
    • No structure of the protein-DNA complex
    • Physiological DNA targets in vivo not mapped
  4. 2007 Low

    Linked Repin1 to metabolic syndrome traits by correlating a 3'-UTR triplet-repeat expansion with VLDL cholesterol, insulin levels, and hepatic expression.

    Evidence DNA sequencing across 9 rat strains with liver/adipose/blood expression analysis and regression

    PMID:17173329

    Open questions at the time
    • Correlative only — no direct functional manipulation of the repeat
    • Causal direction between expression and phenotype not established
    • Single study, no mechanistic link to known DNA-binding function
  5. 2010 Medium

    Provided first functional evidence that REPIN1 controls adipocyte size and glucose/fatty-acid handling, tying it to glucose-transporter expression.

    Evidence siRNA knockdown in mature 3T3-L1 adipocytes with glucose/palmitate uptake assays, triglyceride measurement, and qRT-PCR

    PMID:20727851

    Open questions at the time
    • Whether GLUT1/GLUT4 changes are direct transcriptional targets of REPIN1 was not shown
    • Single cell line
    • No in vivo confirmation
  6. 2014 High

    Demonstrated in vivo that hepatic REPIN1 governs systemic insulin sensitivity and hepatic lipid content, identifying downstream effector molecules.

    Evidence Liver-specific knockout mice with hyperinsulinemic-euglycemic clamp, lipid profiling, Western blot, and qRT-PCR

    PMID:24760138

    Open questions at the time
    • Direct versus indirect regulation of CD36, PPARγ, GLUT2, and lipocalin2 not distinguished
    • Mechanism linking nuclear DNA binding to metabolic gene control unresolved
  7. 2018 Medium

    Showed hepatocellular REPIN1 is required for the transient lipid accumulation that supports liver regeneration, via fatty-acid transporters.

    Evidence Partial hepatectomy in liver-specific KO mice with lipid quantification, Western blot, qRT-PCR, and in vitro hepatocyte steatosis

    PMID:30442920

    Open questions at the time
    • Whether CD36/FATP5 are direct targets not established
    • Single lab
  8. 2023 Medium

    Extended REPIN1 function to osteoblast apoptosis, identifying LCN2 as a downstream effector of iron-overload toxicity.

    Evidence shRNA knockdown in iron-overload osteoporosis mouse model with siRNA/plasmid rescue, apoptosis assays, iron measurement, and clinical specimens

    PMID:37749079

    Open questions at the time
    • Whether REPIN1 binds the LCN2 promoter directly not shown
    • Connection to canonical DNA-binding/replication role unexplored

Open questions

Synthesis pass · forward-looking unresolved questions
  • How REPIN1's sequence-specific zinc-finger DNA-binding activity mechanistically links to its transcriptional control of metabolic genes (CD36, GLUT1/4, LCN2) remains unresolved.
  • No direct genome-wide binding map relating origin binding to metabolic target genes
  • No structural model of the protein-DNA complex
  • Relationship between the replication-initiation role and metabolic roles undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 3 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-1430728 Metabolism 3

Evidence

Reading pass · 8 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 RIP60 (REPIN1) was purified ~9,000-fold from HeLa cell nuclear extract and identified as a 60-kDa polypeptide with origin-specific DNA-binding activity at the Chinese hamster DHFR replication origin and yeast ARS1. Co-purifying fractions also contained an ATP-dependent DNA helicase activity residing in a 100-kDa polypeptide (RIP100), suggesting RIP60 and RIP100 may cooperate in initiation of chromosomal DNA synthesis. Protein purification (5-step chromatography), protein-DNA cross-linking, oligonucleotide displacement assay, ATP covalent radiolabeling Molecular and cellular biology High 2174103
1990 Purified RIP60 markedly enhanced DNA bending of the DHFR origin region (oribeta) sequences containing five oligo(dA)3-4 tract bend elements. RIP60 binds an ATT-rich motif overlapping bend element B5, and its binding accentuates the anomalous migration of circularly permuted DNA fragments, indicating RIP60 promotes DNA bending near the replication origin. Circular permutation assay, gel mobility shift assay with purified RIP60 and circularly permuted bent DNA fragments Molecular and cellular biology High 2247056
2000 Human RIP60 (REPIN1) contains 15 C2H2 zinc finger (ZF) DNA-binding motifs organized in three clusters (Z1: ZFs 1–5; Z2: ZFs 6–8; Z3: ZFs 9–15) plus a proline-rich region between Z2 and Z3. Hands Z1 and Z2 independently bind the oribeta RIP60 sites specifically but with different affinities; hand Z3 binds DNA non-specifically. Hand Z2 plus an adjacent portion of the proline-rich region is sufficient for protein multimerization on DNA and formation of a twisted ~720 bp DNA loop in vitro, as visualized by atomic force microscopy. RIP60 showed only weak replication enhancer activity in polyomavirus origin-dependent plasmid replication assays. One-hybrid yeast screen (cDNA cloning), gel mobility shift assay, DNase I footprinting, ligation enhancement assay, atomic force microscopy, plasmid replication assay Nucleic acids research High 10606657
2007 A triplet repeat (TTT) expansion in the 3'-UTR of Repin1 correlates with metabolic phenotypes including VLDL cholesterol and serum insulin levels across rat strains, and Repin1 expression in liver is significantly associated with repeat size, suggesting the 3'-UTR triplet repeat modulates Repin1 expression and thereby contributes to metabolic syndrome traits. DNA sequencing across 9 rat strains, RNA expression analysis (liver, adipose, blood), linear multiple regression analysis Diabetes/metabolism research and reviews Low 17173329
2010 siRNA-mediated knockdown of Repin1 in mature 3T3-L1 adipocytes significantly reduced adipocyte size, decreased basal glucose uptake, enhanced insulin-stimulated glucose uptake, and reduced palmitate uptake. Repin1 knockdown altered mRNA expression of genes involved in lipid droplet formation, adipogenesis, and glucose and fatty acid transport, including GLUT1 and GLUT4, suggesting Repin1 regulates adipocyte size and glucose transporter expression. siRNA knockdown by electroporation in 3T3-L1 adipocytes, glucose transport assay, palmitate uptake assay, triglyceride content measurement, qRT-PCR Biochemical and biophysical research communications Medium 20727851
2014 Liver-specific knockout of Repin1 (LRep1−/−) in mice resulted in significantly improved whole-body insulin sensitivity (hyperinsulinemic-euglycemic clamp) and lower hepatic triglyceride content. Repin1 deficiency caused significant changes in downstream target molecules including reduced CD36 and PPARγ protein, altered GLUT2 protein, decreased Akt phosphorylation, and changed lipocalin2, Vamp4, and Snap23 mRNA expression. Secondary changes in adipose tissue function were also observed, potentially mediated by altered hepatic lipocalin2 or chemerin expression. Liver-specific knockout mouse generation, hyperinsulinemic-euglycemic clamp, hepatic lipid profiling, Western blot, qRT-PCR Diabetes High 24760138
2018 Liver-specific Repin1 knockout (LRep1−/−) mice exhibited significantly decreased transient hepatic lipid accumulation after partial hepatectomy, associated with decreased expression of fatty acid transporters CD36 and FATP5, altered extent and timing of liver cell proliferation, and smaller lipid droplets in primary hepatocytes in vitro. These results indicate that hepatocellular Repin1 is required for early lipid accumulation in hepatocytes following partial hepatectomy, which facilitates efficient liver regeneration. Partial hepatectomy model in liver-specific Repin1 KO mice, hepatic lipid staining and quantification, Western blot, qRT-PCR, in vitro steatosis in primary hepatocytes Scientific reports Medium 30442920
2023 Knockdown of Repin1 in an iron-overload-induced osteoporosis mouse model rescued bone loss and inhibited osteoblast apoptosis. Mechanistically, Repin1 knockdown decreased expression of LCN2 (lipocalin-2), which ameliorated intracellular iron overload toxicity. LCN2 was identified as a downstream target of REPIN1, and altering LCN2 expression via siRNA or plasmid partially reversed or replicated the anti-iron effect of Repin1 knockdown. BCL2 and BAX levels (mitochondrial apoptosis pathway) were also regulated downstream of Repin1/LCN2. shRNA knockdown in mouse model, siRNA and plasmid rescue experiments, Western blot, iron content measurement, apoptosis assays, clinical specimen analysis Cell death & disease Medium 37749079

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
1992 L-AP4 inhibits calcium currents and synaptic transmission via a G-protein-coupled glutamate receptor. The Journal of neuroscience : the official journal of the Society for Neuroscience 190 1318954
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
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 141 29180427
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
2013 AP4 is a mediator of epithelial-mesenchymal transition and metastasis in colorectal cancer. The Journal of experimental medicine 138 23752226
1992 L-2-amino-4-phosphonobutyrate (L-AP4) is an agonist at the type IV metabotropic glutamate receptor which is negatively coupled to adenylate cyclase. European journal of pharmacology 138 1361913
2008 AP4 encodes a c-MYC-inducible repressor of p21. Proceedings of the National Academy of Sciences of the United States of America 134 18818310
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
1996 Potent antagonists at the L-AP4- and (1S,3S)-ACPD-sensitive presynaptic metabotropic glutamate receptors in the neonatal rat spinal cord. Neuropharmacology 120 9121605
2013 p53-induced miR-15a/16-1 and AP4 form a double-negative feedback loop to regulate epithelial-mesenchymal transition and metastasis in colorectal cancer. Cancer research 117 24285725
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
1995 Distinct presynaptic metabotropic receptors for L-AP4 and CCG1 on GABAergic terminals: pharmacological evidence using novel alpha-methyl derivative mGluR antagonists, MAP4 and MCCG, in the rat thalamus in vivo. Neuroscience 104 7753406
2018 Altered distribution of ATG9A and accumulation of axonal aggregates in neurons from a mouse model of AP-4 deficiency syndrome. PLoS genetics 96 29698489
2001 Functional and physical interactions of the adaptor protein complex AP-4 with ADP-ribosylation factors (ARFs). The EMBO journal 96 11707398
2014 c-Myc-induced transcription factor AP4 is required for host protection mediated by CD8+ T cells. Nature immunology 89 25029552
2018 Transcription factor AP-4 promotes tumorigenic capability and activates the Wnt/β-catenin pathway in hepatocellular carcinoma. Theranostics 85 30026867
2009 The c-MYC-AP4-p21 cascade. Cell cycle (Georgetown, Tex.) 81 19270520
2016 The Transcription Factor AP4 Mediates Resolution of Chronic Viral Infection through Amplification of Germinal Center B Cell Responses. Immunity 79 27566940
2015 The Adaptor Complex AP-4 Regulates Vacuolar Protein Sorting at the trans-Golgi Network by Interacting with VACUOLAR SORTING RECEPTOR1. Plant physiology 73 26546666
2006 A repressor complex, AP4 transcription factor and geminin, negatively regulates expression of target genes in nonneuronal cells. Proceedings of the National Academy of Sciences of the United States of America 72 16924111
2019 Axonal autophagosome maturation defect through failure of ATG9A sorting underpins pathology in AP-4 deficiency syndrome. Autophagy 69 31142229
2018 TRIB2 functions as novel oncogene in colorectal cancer by blocking cellular senescence through AP4/p21 signaling. Molecular cancer 69 30541550
2010 A PIN1 polymorphism that prevents its suppression by AP4 associates with delayed onset of Alzheimer's disease. Neurobiology of aging 65 20580132
1995 Regional and developmental profile of modulation of hippocampal synaptic transmission and LTP by AP4-sensitive mGluRs in vivo. Neuropharmacology 65 8532180
1990 Purification of RIP60 and RIP100, mammalian proteins with origin-specific DNA-binding and ATP-dependent DNA helicase activities. Molecular and cellular biology 61 2174103
1994 Expression of mRNAs of L-AP4-sensitive metabotropic glutamate receptors (mGluR4, mGluR6, mGluR7) in the rat retina. Neuroscience letters 60 8084499
2017 Amyloid precursor protein traffics from the Golgi directly to early endosomes in an Arl5b- and AP4-dependent pathway. Traffic (Copenhagen, Denmark) 59 28000370
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
1996 Decrease in [Ca2+]c but not in cAMP Mediates L-AP4 inhibition of glutamate release: PKC-mediated suppression of this inhibitory pathway. The European journal of neuroscience 50 9081621
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
1999 Reduced function of L-AP4-sensitive metabotropic glutamate receptors in human epileptic sclerotic hippocampus. The European journal of neuroscience 45 10103105
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
1990 RIP60, a mammalian origin-binding protein, enhances DNA bending near the dihydrofolate reductase origin of replication. Molecular and cellular biology 44 2247056
2022 AP4 suppresses DNA damage, chromosomal instability and senescence via inducing MDC1/Mediator of DNA damage Checkpoint 1 and repressing MIR22HG/miR-22-3p. Molecular cancer 41 35624466
1986 A comparison of 2-amino-4-phosphonobutyric acid (AP4) receptors and [3H]AP4 binding sites in the rat brain. Brain research 39 3013370
2017 AP4 modulated by the PI3K/AKT pathway promotes prostate cancer proliferation and metastasis of prostate cancer via upregulating L-plastin. Cell death & disease 37 28981098
2014 Golgi-dependent transport of vacuolar sorting receptors is regulated by COPII, AP1, and AP4 protein complexes in tobacco. The Plant cell 36 24642936
2013 AP4 directly downregulates p16 and p21 to suppress senescence and mediate transformation. Cell death & disease 36 23949224
1988 A new and specific non-NMDA receptor antagonist, FG 9065, blocks L-AP4-evoked depolarization in rat cerebral cortex. European journal of pharmacology 36 2898377
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
1989 Novel recognition site for L-quisqualate sensitizes neurons to depolarization by L-2-amino-4-phosphonobutanoate (L-AP4). Brain research 32 2545307
2017 USP22 drives colorectal cancer invasion and metastasis via epithelial-mesenchymal transition by activating AP4. Oncotarget 31 28427243
1997 The L-AP4 receptor. General pharmacology 31 9251893
2018 AP4 deficiency: A novel form of neurodegeneration with brain iron accumulation? Neurology. Genetics 30 29473051
2012 Down-regulation of AP-4 inhibits proliferation, induces cell cycle arrest and promotes apoptosis in human gastric cancer cells. PloS one 30 22615908
1994 Activation of metabotropic glutamate receptors by L-AP4 stimulates survival of rat cerebellar granule cells in culture. European journal of pharmacology 30 7705463
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
2021 Transcription Factor AP4 Mediates Cell Fate Decisions: To Divide, Age, or Die. Cancers 28 33567514
2018 MicroRNA-302c represses epithelial-mesenchymal transition and metastasis by targeting transcription factor AP-4 in colorectal cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 28 29906744
2011 Transcription factor AP4 modulates reversible and epigenetic silencing of the Cd4 gene. Proceedings of the National Academy of Sciences of the United States of America 28 21873191
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
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
1994 Inhibition of endogenous dopamine release in amphibian retina by L-2-amino-4-phosphonobutyric acid (L-AP4) and trans-2-aminocyclopentane-1,3-dicarboxylate (ACPD). Brain research 27 7525012
1995 Pharmacology of selective and non-selective metabotropic glutamate receptor agonists at L-AP4 receptors in retinal ON bipolar cells. Brain research 25 7796182
2018 AP4 positively regulates LAPTM4B to promote hepatocellular carcinoma growth and metastasis, while reducing chemotherapy sensitivity. Molecular oncology 24 29337428
2016 Molecular Basis for the Interaction Between AP4 β4 and its Accessory Protein, Tepsin. Traffic (Copenhagen, Denmark) 24 26756312
2014 Liver-restricted Repin1 deficiency improves whole-body insulin sensitivity, alters lipid metabolism, and causes secondary changes in adipose tissue in mice. Diabetes 24 24760138
2008 Transcription factor GATA-3 regulates the transcriptional activity of dopamine beta-hydroxylase by interacting with Sp1 and AP4. Neurochemical research 24 18338249
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
2016 MYCN promotes neuroblastoma malignancy by establishing a regulatory circuit with transcription factor AP4. Oncotarget 23 27448979
2015 JQ1, an inhibitor of the epigenetic reader BRD4, suppresses the bidirectional MYC-AP4 axis via multiple mechanisms. Oncology reports 23 26573731
2000 The dhfr oribeta-binding protein RIP60 contains 15 zinc fingers: DNA binding and looping by the central three fingers and an associated proline-rich region. Nucleic acids research 23 10606657
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 22 35976706
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
2010 Repin1 maybe involved in the regulation of cell size and glucose transport in adipocytes. Biochemical and biophysical research communications 22 20727851
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 22 19505873
2007 Triplet repeat in the Repin1 3'-untranslated region on rat chromosome 4 correlates with facets of the metabolic syndrome. Diabetes/metabolism research and reviews 21 17173329
2003 Adenosine tetraphosphate, Ap4, a physiological regulator of intraocular pressure in normotensive rabbit eyes. The Journal of pharmacology and experimental therapeutics 21 14600249
2023 REPIN1 regulates iron metabolism and osteoblast apoptosis in osteoporosis. Cell death & disease 20 37749079
2022 Arsenic trioxide-loaded nanoparticles enhance the chemosensitivity of gemcitabine in pancreatic cancer via the reversal of pancreatic stellate cell desmoplasia by targeting the AP4/galectin-1 pathway. Biomaterials science 20 36052559
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
2018 Ap4 is rate limiting for intestinal tumor formation by controlling the homeostasis of intestinal stem cells. Nature communications 19 30177706
2014 AP4 is required for mitogen- and c-MYC-induced cell cycle progression. Oncotarget 19 25261373
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
1992 Structure-function relationships for analogues of L-2-amino-4-phosphonobutanoic acid on the quisqualic acid-sensitive AP4 receptor of the rat hippocampus. Brain research 18 1327404
1991 A pancreatic exocrine cell factor and AP4 bind overlapping sites in the amylase 2A enhancer. Biochemistry 18 1714299
2018 The Transcription Factor AP4 Promotes Oncogenic Phenotypes and Cisplatin Resistance by Regulating LAPTM4B Expression. Molecular cancer research : MCR 17 29378908
1994 Actions of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) in retinal ON bipolar cells indicate that it is an agonist at L-AP4 receptors. The Journal of general physiology 17 7931135
2023 Diadenosine Tetraphosphate (Ap4 A) Serves as a 5' RNA Cap in Mammalian Cells. Angewandte Chemie (International ed. in English) 16 37934413
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
1991 Characterization of retinal and hippocampal L-AP4 receptors using conformationally constrained AP4 analogues. Brain research 16 1667614
2018 Liver-specific Repin1 deficiency impairs transient hepatic steatosis in liver regeneration. Scientific reports 15 30442920
2014 Crosstalk of AP4 and TGFβ receptor signaling in NSCLC. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 15 25266805
2009 Polarized sorting of AMPA receptors to the somatodendritic domain is regulated by adaptor protein AP-4. Neuroscience research 15 19481121
1998 The group III metabotropic glutamate receptor agonist, l-AP4, reduces EPSPs in some layers of rat visual cortex. Brain research 15 9666134
2015 AP4 activates cell migration and EMT mediated by p53 in MDA-MB-231 breast carcinoma cells. Molecular and cellular biochemistry 14 26037074
2011 The epsilon hinge-ear region regulates membrane localization of the AP-4 complex. Traffic (Copenhagen, Denmark) 14 21810154
2003 Changes of mGluR4 and the effects of its specific agonist L-AP4 in a rodent model of diffuse brain injury. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 14 14592619
1991 Comparative activity of doxorubicin and its major metabolite, doxorubicinol, on V79/AP4 fibroblasts: a morphofunctional study. Experimental and molecular pathology 14 1748213

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