Affinage

ARID4B

AT-rich interactive domain-containing protein 4B · UniProt Q4LE39

Length
1312 aa
Mass
147.8 kDa
Annotated
2026-04-28
100 papers in source corpus 14 papers cited in narrative 14 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ARID4B is a chromatin-regulatory protein that operates within the SIN3A–HDAC1 complex to modulate histone modifications—including H3K27ac, H3K27me3, H3K4me3, H3K9me3, and H4K20me3—at developmental, imprinted, and oncogenic loci, thereby controlling transcriptional programs required for embryonic stem cell differentiation toward mesoderm/endoderm lineages, genomic imprinting at the PWS/AS locus, and hematopoietic homeostasis (PMID:33454011, PMID:17043311, PMID:18728284). ARID4B physically interacts with ARID4A and RB and functions as a transcriptional coactivator for androgen receptor in Sertoli cells, where it is essential for spermatogenesis, blood–testis barrier integrity, and establishment of the spermatogonial stem cell niche (PMID:23487765, PMID:26258622, PMID:28207192). In PTEN-deficient prostate cancer, ARID4B directly binds the PIK3CA and PIK3R2 promoters to sustain PI3K/AKT signaling, and it similarly activates the mTOR promoter by promoting H3K27 acetylation, establishing ARID4B as a chromatin-dependent transcriptional activator of the PI3K–AKT–mTOR axis (PMID:31551414, PMID:34881695). Arid4b haploinsufficiency cooperates with Arid4a loss to accelerate acute myeloid leukemia in mice, and its expression is post-transcriptionally regulated by multiple miRNAs including miR-290-3p and miR-519b-3p (PMID:18728284, PMID:23447578, PMID:29477868).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2006 High

    The question of whether ARID4B participates in epigenetic regulation of genomic imprinting was answered: combined Arid4a/Arid4b deficiency altered histone methylation and DNA methylation at the PWS imprinting center, establishing both proteins as chromatin regulators of imprinted loci acting through RB.

    Evidence Gene-trap and knockout mice with co-IP, chromatin modification assays, and genetic epistasis with AS-IC mutation

    PMID:17043311

    Open questions at the time
    • Whether ARID4B directly binds the PWS-IC or acts indirectly through RB
    • Structural basis of ARID4A–ARID4B interaction
    • Whether ARID4B has independent functions at imprinted loci apart from ARID4A
  2. 2008 High

    Whether ARID4B cooperates with ARID4A in tumor suppression was resolved: Arid4b haploinsufficiency dramatically accelerated the progression from myeloproliferative disorder to AML in Arid4a-null mice, linking both proteins to hematopoietic homeostasis via histone methylation of Hox gene loci.

    Evidence Mouse knockout/haploinsufficiency models with histology, flow cytometry, and histone mark analysis in bone marrow

    PMID:18728284

    Open questions at the time
    • Whether ARID4B loss alone is sufficient for leukemogenesis
    • Direct genomic targets of ARID4B in hematopoietic progenitors
    • Mechanism by which histone trimethylation changes regulate Hox gene expression
  3. 2012 High

    The molecular complex context of ARID4B was clarified: ARID4B physically interacts with BRMS1, mSIN3A, and mSDS3, placing it in the SIN3A–HDAC complex, and its expression promotes breast cancer metastasis through the Tpx2 gene network.

    Evidence Reciprocal co-IP for protein interactions, shRNA knockdown in MMTV-PyMT mouse model, gene expression profiling

    PMID:22693453

    Open questions at the time
    • Whether ARID4B directly regulates Tpx2 transcription or acts indirectly
    • Allelic variant effects on HDAC complex stoichiometry in vivo
  4. 2013 High

    ARID4B was established as a transcriptional coactivator for androgen receptor and RB in Sertoli cells: combined Arid4a/Arid4b deficiency phenocopied AR and RB knockouts, causing spermatogenic arrest and blood–testis barrier defects.

    Evidence Mouse knockout models, co-IP, AR/RB target gene expression analysis, histology and barrier permeability assays

    PMID:23487765

    Open questions at the time
    • Whether ARID4B coactivator function depends on its ARID domain DNA binding
    • Whether ARID4B acts as coactivator in tissues other than Sertoli cells
  5. 2013 Medium

    Post-transcriptional regulation of ARID4B was demonstrated: miR-290-3p directly targets the ARID4B 3'UTR, suppressing its expression and thereby inhibiting breast cancer progression.

    Evidence Luciferase reporter assay for direct 3'UTR targeting, in vivo tumor/metastasis models

    PMID:23447578

    Open questions at the time
    • Physiological contexts in which miR-290-3p regulates ARID4B beyond breast cancer
    • Quantitative contribution of miR-290-3p versus other miRNAs to ARID4B regulation
  6. 2015 High

    The cell-autonomous requirement for ARID4B in male fertility was defined: Sertoli cell-specific Arid4b knockout caused complete infertility with spermatogenic arrest, confirming ARID4B as essential for AR coactivation of Rhox5 and Sertoli cell maturation.

    Evidence Sertoli cell-specific conditional knockout mice, histology, AR coactivation assay

    PMID:26258622

    Open questions at the time
    • Whether ARID4B binds Rhox5 regulatory regions directly
    • Genome-wide AR-dependent targets requiring ARID4B coactivation in Sertoli cells
  7. 2017 High

    ARID4B's role was extended from spermatogenesis to stem cell niche establishment: its loss in Sertoli cells caused failure to establish the spermatogonial stem cell niche, with defective expression of niche factors (GDNF, KIT ligand, gap junction proteins).

    Evidence Sertoli cell-specific conditional knockout, gene expression profiling, cell fate analysis

    PMID:28207192

    Open questions at the time
    • Whether ARID4B directly binds niche gene promoters or acts through intermediate regulators
    • Whether ARID4B regulates stem cell niches in other tissues
  8. 2018 Medium

    Additional miRNA regulators of ARID4B were identified: miR-519b-3p directly binds ARID4B 3'UTR to modulate chemoradiation sensitivity in rectal cancer, and miR-30d expression negatively correlates with ARID4B in prostate cancer.

    Evidence Luciferase reporter assays (miR-519b-3p), miRNA-mRNA correlation and functional knockout (miR-30d)

    PMID:29477868 PMID:29797600

    Open questions at the time
    • miR-30d targeting of ARID4B lacks direct luciferase validation
    • Relative contribution of different miRNAs to ARID4B protein levels in individual cancer types
  9. 2019 High

    The mechanism by which ARID4B sustains PI3K/AKT signaling in PTEN-deficient tumors was resolved: ARID4B directly binds PIK3CA and PIK3R2 promoters, competing with histone H1 to maintain open chromatin, and is specifically required for prostate tumorigenesis when PTEN is lost.

    Evidence ChIP for direct promoter binding, loss-of-function epistasis with PTEN, in vivo tumorigenesis models, patient data

    PMID:31551414

    Open questions at the time
    • Whether ARID4B–histone H1 competition is a general mechanism at other ARID4B targets
    • Structural basis for ARID4B promoter recognition at PIK3CA/PIK3R2
  10. 2020 High

    ARID4B's role in pluripotent cell differentiation was established: it is required for mesoderm/endoderm lineage commitment of mESCs, physically and functionally interacts with HDAC1 (not HDAC2) within SIN3A, and its loss causes redistribution of H3K27me3/H3K27ac at developmental loci.

    Evidence Pooled epigenetic shRNA screen, conditional knockout mESCs, co-IP, ChIP-seq for H3K27me3/H3K27ac

    PMID:33454011

    Open questions at the time
    • Why ARID4B selectively interacts with HDAC1 but not HDAC2
    • How ARID4B loss both increases and decreases H3K27ac at different loci
    • Identity of direct ARID4B-bound genomic sites genome-wide
  11. 2021 Medium

    ARID4B was shown to directly activate the mTOR promoter by promoting H3K27ac at a specific upstream site, placing it as a chromatin effector in the PI3K→ARID4B→mTOR signaling axis in myoblasts.

    Evidence ChIP-PCR/ChIP-qPCR for mTOR promoter binding, siRNA knockdown and dCas9 activation epistasis, PI3K inhibitor treatment

    PMID:34881695

    Open questions at the time
    • Whether ARID4B-mediated mTOR promoter activation operates in cell types beyond myoblasts
    • Whether HDAC1/SIN3A complex is involved at the mTOR promoter
    • Mechanism by which PI3K activity induces ARID4B expression

Open questions

Synthesis pass · forward-looking unresolved questions
  • A genome-wide map of direct ARID4B binding sites, the structural basis for its ARID domain specificity, and whether its coactivator versus repressor functions are context-dependent or reflect distinct complex compositions remain unresolved.
  • No genome-wide ARID4B ChIP-seq in any cell type
  • No structural model of ARID4B or its ARID domain bound to DNA
  • Mechanism determining whether ARID4B promotes or removes H3K27ac at specific loci

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0042393 histone binding 4 GO:0003677 DNA binding 2
Localization
GO:0005634 nucleus 3 GO:0005694 chromosome 2
Pathway
R-HSA-4839726 Chromatin organization 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3
Partners
ARARID4ABRMS1HDAC1RB1SDS3SIN3A
Complex memberships
SIN3A-HDAC1 complex

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 RBBP1/ARID4A interacts physically with RBBP1L1/ARID4B and with the Snrpn promoter, and combined deficiency of Arid4a and Arid4b alters epigenetic modifications (reduced trimethylation of H4K20 and H3K9, reduced DNA methylation) at the PWS-IC, changing the maternal allele toward a more paternal epigenotype; mutations in Arid4a, Arid4b, or Rb suppressed an Angelman syndrome imprinting defect caused by a mutation at the AS-IC. Gene trap mutagenesis, gene knockout mice, western blotting, immunofluorescence, co-immunoprecipitation/promoter interaction assays, genetic epistasis Genes & development High 17043311
2008 Arid4a-deficient mice progressed from ineffective hematopoiesis to CMML-like myeloproliferative disorder to AML; haploinsufficiency of Arid4b dramatically accelerated AML development (10/12 double-mutant mice vs 5/42 Arid4a-/- alone). Loss of Arid4a increased histone trimethylation of H3K4, H3K9, and H4K20 in bone marrow, and decreased expression of Hox genes (Hoxb3, b5, b6, b8) and FoxP3. Mouse knockout/haploinsufficiency models, complete blood counts, flow cytometry, histology, RT-PCR, western blotting, immunofluorescence Journal of the National Cancer Institute High 18728284
2012 ARID4B physically interacts with breast cancer metastasis suppressor BRMS1 and with histone deacetylase complex members mSIN3A and mSDS3; allelic variants of Arid4b show differential binding to these HDAC complex members. Ectopic Arid4b expression promoted primary tumor growth and increased cell migration/invasion, while shRNA-mediated knockdown reduced pulmonary metastases and downregulated the Tpx2 gene network regulating cell cycle and mitotic spindle biology. Co-immunoprecipitation, shRNA knockdown in vivo (mouse MMTV-PyMT model), ectopic overexpression, in vitro migration/invasion assays, gene expression profiling PLoS genetics High 22693453
2013 ARID4A and ARID4B physically interact with each other; ARID4A is a retinoblastoma (RB)-binding protein. In Sertoli cells, ARID4A and ARID4B function as transcriptional coactivators for androgen receptor (AR) and RB, regulating downstream AR- and RB-responsive genes. Combined deficiency causes spermatogenic arrest, impaired blood-testis barrier, and seminal vesicle agenesis/hypodysplasia, phenocopying Sertoli cell-specific AR and RB knockouts. Mouse knockout/haploinsufficiency models, physical interaction assays (co-IP), gene expression analysis of AR/RB downstream targets, histology, blood-testis barrier permeability assay Proceedings of the National Academy of Sciences of the United States of America High 23487765
2013 miR-290-3p directly targets the 3' UTR of Arid4b mRNA (confirmed by luciferase reporter assay), suppressing ARID4B expression and thereby suppressing breast cancer progression; miR-290 upregulation also elevated estrogen receptor levels, increasing apoptosis. miRNA microarray, luciferase reporter assay, in vivo tumor/metastasis models, pathway analysis Cancer research Medium 23447578
2015 ARID4B functions as a coactivator of androgen receptor (AR) in Sertoli cells and is required for optimal transcriptional activation of reproductive homeobox 5 (Rhox5), an AR target gene. Sertoli cell-specific Arid4b knockout mice are completely infertile with Sertoli cell-only phenotype, germ cell loss, and spermatogenic arrest at the round spermatid stage; Sertoli cell maturation is delayed. Sertoli cell-specific conditional knockout mice, histology, immunofluorescence, gene expression analysis, AR coactivation assay Molecular endocrinology High 26258622
2017 In Sertoli cell-specific Arid4b knockout testes, ARID4B ablation causes abnormal Sertoli cell detachment from the basement membrane during the gonocyte-to-SSC transition, failure to establish the stem cell niche, gonocyte apoptosis, and impaired SSC self-renewal. ARID4B regulates downstream niche genes including gap junction protein alpha-1, KIT ligand, AMH, GDNF, inhibin alpha/beta, and Cyp26b1. Sertoli cell-specific conditional knockout mice, gene expression profiling, histology, cell fate analysis Stem cells High 28207192
2019 PTEN inhibits expression of ARID4B; ARID4B acts as a transcriptional activator of PI3K subunit genes PIK3CA and PIK3R2 by binding their promoters; reciprocal binding of ARID4B and histone H1 to PIK3CA and PIK3R2 promoters modulates chromatin condensation. ARID4B is required for prostate tumorigenesis specifically when PTEN is deficient, defining a PTEN-ARID4B-PI3K axis. Chromatin immunoprecipitation (ChIP), promoter binding assays, loss-of-function experiments, gene expression analysis, in vivo tumorigenesis models, patient data analysis Nature communications High 31551414
2020 ARID4B is critical for mouse embryonic stem cell differentiation toward mesodermal and endodermal lineages. Arid4b-deficient mESCs self-renew normally but fail to upregulate meso/endodermal gene expression programs. ARID4B physically and functionally interacts with HDAC1 (but not HDAC2) within the SIN3A complex. ARID4B deficiency leads to increased H3K27me3 and reduced H3K27Ac at key developmental gene loci, while a subset of regions gain H3K27Ac. Pooled epigenetic shRNA screen, conditional knockout mESCs, differentiation assays, co-immunoprecipitation, ChIP-seq for H3K27me3/H3K27Ac, gene expression profiling The Journal of biological chemistry High 33454011
2018 miR-30d directly regulates ARID4B (and ARID4A) expression in prostate cancer; mRNA expression of miR-30d is significantly negatively correlated with ARID4B. Knockout of ARID4B promoted prostate cancer cell proliferation, migration, and invasion in vitro, supporting a tumor suppressor function. miRNA-mRNA correlation in patient tissues, in vitro knockout, proliferation/migration/invasion assays Journal of cellular biochemistry Medium 29797600
2018 miR-519b-3p directly binds the 3' UTR of ARID4B mRNA and negatively regulates its expression; overexpression of miR-519b-3p enhanced responsiveness to chemoradiation in rectal cancer cells in an ARID4B-dependent manner. Luciferase reporter assay, overexpression/knockdown in vitro, patient tissue correlation Gene Medium 29477868
2020 Circ-SMARCA5 functions as a tumor suppressor in colorectal cancer by sponging miR-93-3p (predicted as miR-39-3p in abstract), thereby upregulating ARID4B expression; this axis inhibits CRC cell proliferation, migration, and invasion in vitro and tumor progression in vivo. qRT-PCR, luciferase reporter assay, overexpression, CCK-8/wound healing/Transwell assays, xenograft model Digestive and liver disease Medium 32807692
2021 ARID4B knockdown in human glioma cells suppressed PI3K/AKT/mTOR pathway components (p-mTOR, p-PI3K, p-AKT), caused G1 phase arrest by downregulating Cyclin D1, increased HDAC1 expression leading to elevated acetyl-p53 and acetyl-H3 levels, and induced apoptosis; it also reduced glioma cell migration and invasion. Lentiviral shRNA knockdown, western blotting, flow cytometry (cell cycle/apoptosis), proliferation assay, migration/invasion assay OncoTargets and therapy Medium 33732001
2021 Taurine promotes protein synthesis and proliferation of C2C12 myoblast cells through the PI3K-ARID4B-mTOR pathway; ARID4B expression is induced by taurine in a PI3K-dependent manner. ARID4B binds to the -4368 to -4591 bp site of the mTOR promoter (confirmed by ChIP-PCR), promoting H3K27ac (but not H3K27me3) at this site, and ARID4B knockdown abolishes taurine-stimulated mTOR expression and mTOR phosphorylation. siRNA knockdown, CRISPR/dCas9 gene activation, ChIP-PCR and ChIP-qPCR, PI3K inhibitor (LY294002), western blotting, proliferation assay The British journal of nutrition Medium 34881695

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 Cancer progression by reprogrammed BCAA metabolism in myeloid leukaemia. Nature 329 28514443
2010 Adipose tissue branched chain amino acid (BCAA) metabolism modulates circulating BCAA levels. The Journal of biological chemistry 315 20093359
2018 The BCKDH Kinase and Phosphatase Integrate BCAA and Lipid Metabolism via Regulation of ATP-Citrate Lyase. Cell metabolism 282 29779826
2019 Targeting BCAA Catabolism to Treat Obesity-Associated Insulin Resistance. Diabetes 262 31167878
2004 Exercise promotes BCAA catabolism: effects of BCAA supplementation on skeletal muscle during exercise. The Journal of nutrition 261 15173434
2019 Loss of BCAA Catabolism during Carcinogenesis Enhances mTORC1 Activity and Promotes Tumor Development and Progression. Cell metabolism 249 30661928
2020 BCAT2-mediated BCAA catabolism is critical for development of pancreatic ductal adenocarcinoma. Nature cell biology 202 32029896
2022 Role of branched-chain amino acid metabolism in the pathogenesis of obesity and type 2 diabetes-related metabolic disturbances BCAA metabolism in type 2 diabetes. Nutrition & diabetes 197 35931683
2019 Loss of EZH2 Reprograms BCAA Metabolism to Drive Leukemic Transformation. Cancer discovery 148 31189531
2023 METTL16 drives leukemogenesis and leukemia stem cell self-renewal by reprogramming BCAA metabolism. Cell stem cell 135 36608679
2018 BCAA Metabolism and Insulin Sensitivity - Dysregulated by Metabolic Status? Molecular nutrition & food research 133 29377510
2014 Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism. Cell metabolism 120 25307860
2020 Acetylation promotes BCAT2 degradation to suppress BCAA catabolism and pancreatic cancer growth. Signal transduction and targeted therapy 106 32467562
2022 BCAA-BCKA axis regulates WAT browning through acetylation of PRDM16. Nature metabolism 87 35075301
2006 Deficiency of Rbbp1/Arid4a and Rbbp1l1/Arid4b alters epigenetic modifications and suppresses an imprinting defect in the PWS/AS domain. Genes & development 83 17043311
2008 Identification of chromatin remodeling genes Arid4a and Arid4b as leukemia suppressor genes. Journal of the National Cancer Institute 74 18728284
2024 BCAA-nitrogen flux in brown fat controls metabolic health independent of thermogenesis. Cell 68 38653240
2024 The role of BCAA metabolism in metabolic health and disease. Experimental & molecular medicine 68 38956299
2023 Enhanced BCAT1 activity and BCAA metabolism promotes RhoC activity in cancer progression. Nature metabolism 68 37337119
2020 Muscle-Liver Trafficking of BCAA-Derived Nitrogen Underlies Obesity-Related Glycine Depletion. Cell reports 68 33176135
2022 A randomized placebo-controlled clinical trial for pharmacological activation of BCAA catabolism in patients with type 2 diabetes. Nature communications 67 35717342
2021 Krüppel-like factor 6-mediated loss of BCAA catabolism contributes to kidney injury in mice and humans. Proceedings of the National Academy of Sciences of the United States of America 64 34074766
2020 Phosphorylation of BCKDK of BCAA catabolism at Y246 by Src promotes metastasis of colorectal cancer. Oncogene 63 32238881
2024 BCAA-producing Clostridium symbiosum promotes colorectal tumorigenesis through the modulation of host cholesterol metabolism. Cell host & microbe 62 39106870
2017 Krüppel-like factor 15: Regulator of BCAA metabolism and circadian protein rhythmicity. Pharmacological research 61 29288718
2001 BCAA intake affects protein metabolism in muscle after but not during exercise in humans. American journal of physiology. Endocrinology and metabolism 60 11440914
2013 ARID4A and ARID4B regulate male fertility, a functional link to the AR and RB pathways. Proceedings of the National Academy of Sciences of the United States of America 59 23487765
2017 BCKDK of BCAA Catabolism Cross-talking With the MAPK Pathway Promotes Tumorigenesis of Colorectal Cancer. EBioMedicine 56 28501528
2022 Mitochondrial H2S Regulates BCAA Catabolism in Heart Failure. Circulation research 53 35701874
2019 Associations Between Dietary Protein Sources, Plasma BCAA and Short-Chain Acylcarnitine Levels in Adults. Nutrients 52 30650556
2018 Dietary Pattern and Plasma BCAA-Variations in Healthy Men and Women-Results from the KarMeN Study. Nutrients 49 29762522
2017 Anti-inflammatory and anti-genotoxic activity of branched chain amino acids (BCAA) in lipopolysaccharide (LPS) stimulated RAW 264.7 macrophages. Food science and biotechnology 49 30263672
2023 Branched-chain amino acid catabolism in muscle affects systemic BCAA levels but not insulin resistance. Nature metabolism 45 37100997
2019 BCAA Catabolic Defect Alters Glucose Metabolism in Lean Mice. Frontiers in physiology 45 31551816
2016 BCAA Metabolism and NH3 Homeostasis. Advances in neurobiology 45 27885628
2012 Allelic variation and differential expression of the mSIN3A histone deacetylase complex gene Arid4b promote mammary tumor growth and metastasis. PLoS genetics 45 22693453
2011 BRCAA1 monoclonal antibody conjugated fluorescent magnetic nanoparticles for in vivo targeted magnetofluorescent imaging of gastric cancer. Journal of nanobiotechnology 45 21612621
2019 PP2Cm overexpression alleviates MI/R injury mediated by a BCAA catabolism defect and oxidative stress in diabetic mice. European journal of pharmacology 44 31738932
2023 BCAA insufficiency leads to premature ovarian insufficiency via ceramide-induced elevation of ROS. EMBO molecular medicine 42 36847712
2019 Identification of the PTEN-ARID4B-PI3K pathway reveals the dependency on ARID4B by PTEN-deficient prostate cancer. Nature communications 39 31551414
2005 Usefulness of granular BCAA after hepatectomy for liver cancer complicated with liver cirrhosis. Nutrition (Burbank, Los Angeles County, Calif.) 39 15811769
1991 Effect of glucose and branched chain amino acid (BCAA) infusion on onset of liver regeneration and plasma amino acid pattern in partially hepatectomized rats. Journal of hepatology 39 1918875
2013 Inherited variation in miR-290 expression suppresses breast cancer progression by targeting the metastasis susceptibility gene Arid4b. Cancer research 37 23447578
1988 Pharmacological reversal of abnormal glucose regulation, BCAA utilization, and muscle catabolism in sepsis by dichloroacetate. The Journal of trauma 36 3418755
2001 RBP1L1, a retinoblastoma-binding protein-related gene encoding an antigenic epitope abundantly expressed in human carcinomas and normal testis. Journal of the National Cancer Institute 35 11481388
2024 BCAA mediated microbiota-liver-heart crosstalk regulates diabetic cardiomyopathy via FGF21. Microbiome 33 39182099
2020 Circ-SMARCA5 suppresses colorectal cancer progression via downregulating miR-39-3p and upregulating ARID4B. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 31 32807692
2016 Metformin inhibits Branched Chain Amino Acid (BCAA) derived ketoacidosis and promotes metabolic homeostasis in MSUD. Scientific reports 31 27373929
2023 Impaired BCAA catabolism in adipose tissues promotes age-associated metabolic derangement. Nature aging 30 37488415
2023 Targeting BCAA metabolism to potentiate metformin's therapeutic efficacy in the treatment of diabetes in mice. Diabetologia 30 37581618
2022 Elevated BCAA Suppresses the Development and Metastasis of Breast Cancer. Frontiers in oncology 30 35785192
2018 BCAT1 promotes proliferation of endometrial cancer cells through reprogrammed BCAA metabolism. International journal of clinical and experimental pathology 30 31949641
2021 Metabolic flexibility via mitochondrial BCAA carrier SLC25A44 is required for optimal fever. eLife 29 33944778
2024 CPT1A loss disrupts BCAA metabolism to confer therapeutic vulnerability in TP53-mutated liver cancer. Cancer letters 27 38823763
2017 Effect of BCAA supplement timing on exercise-induced muscle soreness and damage: a pilot placebo-controlled double-blind study. The Journal of sports medicine and physical fitness 27 28944645
2024 Attenuating Muscle Damage Biomarkers and Muscle Soreness After an Exercise-Induced Muscle Damage with Branched-Chain Amino Acid (BCAA) Supplementation: A Systematic Review and Meta-analysis with Meta-regression. Sports medicine - open 26 38625669
2021 PPARγ-induced upregulation of subcutaneous fat adiponectin secretion, glyceroneogenesis and BCAA oxidation requires mTORC1 activity. Biochimica et biophysica acta. Molecular and cell biology of lipids 26 34004356
2011 Effect of Oral Supplementation with Branched-chain Amino Acid (BCAA) during Radiotherapy in Patients with Hepatocellular Carcinoma: A Double-Blind Randomized Study. Cancer research and treatment 26 21509160
2001 Plasma lactate, GH and GH-binding protein levels in exercise following BCAA supplementation in athletes. Amino acids 26 11310926
2021 Effect of Training-Detraining Phases of Multicomponent Exercises and BCAA Supplementation on Inflammatory Markers and Albumin Levels in Frail Older Persons. Nutrients 24 33800577
2004 Characterization of BRCAA1 and its novel antigen epitope identification. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 24 15247124
1992 Oral BCAA supplementation in cirrhosis with chronic encephalopathy: effects on prolactin and estradiol levels. Hepato-gastroenterology 23 1459529
2023 Disrupted cardiac fibroblast BCAA catabolism contributes to diabetic cardiomyopathy via a periostin/NAP1L2/SIRT3 axis. Cellular & molecular biology letters 22 37993768
2023 β-aminoisobutyrics acid, a metabolite of BCAA, activates the AMPK/Nrf-2 pathway to prevent ferroptosis and ameliorates lung ischemia-reperfusion injury. Molecular medicine (Cambridge, Mass.) 22 38049750
2020 Excessive BCAA regulates fat metabolism partially through the modification of m6A RNA methylation in weanling piglets. Nutrition & metabolism 22 31998401
2019 Effect of metformin on myotube BCAA catabolism. Journal of cellular biochemistry 22 31385363
2017 Effect of decreased BCAA synthesis through disruption of ilvC gene on the virulence of Streptococcus pneumoniae. Archives of pharmacal research 22 28735462
2011 Effects of BCAA, arginine and carbohydrate combined drink on post-exercise biochemical response and psychological condition. The Chinese journal of physiology 22 21789887
2003 The effects of the formula of amino acids enriched BCAA on nutritional support in traumatic patients. World journal of gastroenterology 22 12632526
2018 miR-519b-3p promotes responsiveness to preoperative chemoradiotherapy in rectal cancer patients by targeting ARID4B. Gene 20 29477868
2016 Liver BCATm transgenic mouse model reveals the important role of the liver in maintaining BCAA homeostasis. The Journal of nutritional biochemistry 20 27886623
2024 BCAA metabolism in pancreatic cancer affects lipid balance by regulating fatty acid import into mitochondria. Cancer & metabolism 19 38532464
2021 A higher bacterial inward BCAA transport driven by Faecalibacterium prausnitzii is associated with lower serum levels of BCAA in early adolescents. Molecular medicine (Cambridge, Mass.) 19 34525937
2014 BRCAA1 antibody- and Her2 antibody-conjugated amphiphilic polymer engineered CdSe/ZnS quantum dots for targeted imaging of gastric cancer. Nanoscale research letters 19 24940175
2018 Downregulation of ARID4A and ARID4B promote tumor progression and directly regulated by microRNA-30d in patient with prostate cancer. Journal of cellular biochemistry 18 29797600
2014 Effects of Supplementation with BCAA and L-glutamine on Blood Fatigue Factors and Cytokines in Juvenile Athletes Submitted to Maximal Intensity Rowing Performance. Journal of physical therapy science 17 25202189
2023 Fecal microbiome transplantation and tributyrin improves early cardiac dysfunction and modifies the BCAA metabolic pathway in a diet induced pre-HFpEF mouse model. Frontiers in cardiovascular medicine 16 36844730
2022 Mild Endurance Exercise during Fasting Increases Gastrocnemius Muscle and Prefrontal Cortex Thyroid Hormone Levels through Differential BHB and BCAA-Mediated BDNF-mTOR Signaling in Rats. Nutrients 16 35334826
2021 Aberrant BCAA and glutamate metabolism linked to regional neurodegeneration in a mouse model of Leigh syndrome. Biochimica et biophysica acta. Molecular basis of disease 16 33486097
2021 ARID4B Knockdown Suppresses PI3K/AKT Signaling and Induces Apoptosis in Human Glioma Cells. OncoTargets and therapy 16 33732001
2020 ARID4B is critical for mouse embryonic stem cell differentiation towards mesoderm and endoderm, linking epigenetics to pluripotency exit. The Journal of biological chemistry 16 33454011
2016 ARID4B is a good biomarker to predict tumour behaviour and decide WHO grades in gliomas and meningiomas. Journal of clinical pathology 16 27451434
2021 AICAR stimulates mitochondrial biogenesis and BCAA catabolic enzyme expression in C2C12 myotubes. Biochimie 15 34798200
2015 Androgen Receptor Coactivator ARID4B Is Required for the Function of Sertoli Cells in Spermatogenesis. Molecular endocrinology (Baltimore, Md.) 15 26258622
2014 Two randomized controlled studies comparing the nutritional benefits of branched-chain amino acid (BCAA) granules and a BCAA-enriched nutrient mixture for patients with esophageal varices after endoscopic treatment. Journal of gastroenterology 15 24633624
2004 Administration of granulated BCAA and quality of life. Hepatology research : the official journal of the Japan Society of Hepatology 15 15607138
2023 Convergent genomic diversity and novel BCAA metabolism in intrahepatic cholangiocarcinoma. British journal of cancer 14 37076565
2021 Taurine stimulates protein synthesis and proliferation of C2C12 myoblast cells through the PI3K-ARID4B-mTOR pathway. The British journal of nutrition 14 34881695
2013 Characterization of BcaA, a putative classical autotransporter protein in Burkholderia pseudomallei. Infection and immunity 14 23340315
2024 Small-molecule targeting BCAT1-mediated BCAA metabolism inhibits the activation of SHOC2-RAS-ERK to induce apoptosis of Triple-negative breast cancer cells. Journal of advanced research 13 39490614
2023 Loss of BCAA catabolism enhances Rab1A-mTORC1 signaling activity and promotes tumor proliferation in NSCLC. Translational oncology 13 37216755
2022 Prepregnancy Protein Source and BCAA Intake Are Associated with Gestational Diabetes Mellitus in the CARDIA Study. International journal of environmental research and public health 13 36361016
2021 Gentamicin Induced Microbiome Adaptations Associate With Increased BCAA Levels and Enhance Severity of Influenza Infection. Frontiers in immunology 13 33708192
2020 Moderate intake of BCAA-rich protein improves glucose homeostasis in high-fat-fed mice. The Journal of nutritional biochemistry 13 32217465
2019 A high-protein diet, not isolated BCAA, is associated with skeletal muscle mass index in patients with gastrointestinal cancer. Nutrition (Burbank, Los Angeles County, Calif.) 13 32007808
2017 Temporal-Spatial Establishment of Initial Niche for the Primary Spermatogonial Stem Cell Formation Is Determined by an ARID4B Regulatory Network. Stem cells (Dayton, Ohio) 13 28207192
2015 Dexamethasone and BCAA Failed to Modulate Muscle Mass and mTOR Signaling in GH-Deficient Rats. PloS one 13 26086773
2011 Changes in transcription during recovery from heat injury in Salmonella typhimurium and effects of BCAA on recovery. Amino acids 13 21584761
2004 Nocturnal energy and BCAA supplementation in patients with liver cirrhosis. Hepatology research : the official journal of the Japan Society of Hepatology 13 15607141
2022 Evaluation of therapeutic strategies targeting BCAA catabolism using a systems pharmacology model. Frontiers in pharmacology 12 36518669