Affinage

ARID4B

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

Length
1312 aa
Mass
147.8 kDa
Annotated
2026-06-09
100 papers in source corpus 16 papers cited in narrative 16 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ARID4B is a chromatin-associated transcriptional regulator that operates within histone-modifying complexes to control developmental, reproductive, and oncogenic gene programs (PMID:17043311, PMID:33454011). It physically partners with its paralog ARID4A and, together with that protein, functions in epigenetic complexes that maintain repressive histone trimethylation (H3K9, H4K20) and DNA methylation at imprinted loci such as the PWS/AS domain, where combined Arid4a/Arid4b deficiency shifts the maternal allele toward a paternal epigenotype (PMID:17043311). Within the SIN3A complex, ARID4B interacts specifically with HDAC1 (and not HDAC2) and with the corepressor components mSIN3A/mSDS3, and its activity governs the balance of H3K27 acetylation versus H3K27 trimethylation at developmental gene loci, where it is required for embryonic stem cell differentiation toward mesoderm and endoderm (PMID:33454011, PMID:22693453). ARID4A and ARID4B act as transcriptional coactivators for the androgen receptor (AR) and the retinoblastoma protein (RB); in Sertoli cells, ARID4B is required for AR-dependent activation of target genes including Rhox5, and its loss causes complete male infertility with spermatogenic arrest, blood-testis barrier defects, and failure of spermatogonial stem cell niche establishment through dysregulation of effectors such as GDNF, KIT ligand, and CYP26B1 (PMID:23487765, PMID:26258622, PMID:28207192). In cancer, ARID4B binds directly to the promoters of PI3K pathway genes — PIK3CA, PIK3R2, and mTOR — where it competes with histone H1 to modulate chromatin condensation and deposits activating H3K27ac, thereby driving PI3K/AKT/mTOR signaling; this places ARID4B downstream of PTEN as a required factor for prostate tumorigenesis and as a context-dependent regulator of tumor growth and metastasis (PMID:31551414, PMID:34881695, PMID:22693453). ARID4B expression is post-transcriptionally constrained by multiple microRNAs targeting its 3'UTR (PMID:23447578, PMID:29477868).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2001 Medium

    Established ARID4B as a distinct gene product related to but separate from the retinoblastoma-binding protein RBP1/ARID4A, defining the molecular identity of the protein.

    Evidence cDNA library screening and immunoperoxidase staining in MCF-7 breast cancer cells

    PMID:11481388 PMID:15247124

    Open questions at the time
    • Cytoplasmic localization reported by IHC conflicts with later chromatin/nuclear function; no functional mechanism defined
    • Sequence relationship to ARID4A asserted without functional consequence
  2. 2006 High

    Showed ARID4B physically partners with ARID4A in an epigenetic complex that maintains imprinting, answering whether the two paralogs act together at chromatin.

    Evidence Mouse gene-trap genetics, ChIP at the Snrpn promoter, histone modification Western blots, and bisulfite sequencing at the PWS-IC

    PMID:17043311

    Open questions at the time
    • Direct ARID4B-ARID4A binding inferred from complex membership rather than demonstrated by reciprocal Co-IP in this study
    • Mechanism by which the complex directs H4K20/H3K9 methylation not resolved
  3. 2008 High

    Defined ARID4A/ARID4B as leukemia suppressors that control hematopoietic gene expression through histone trimethylation, extending their epigenetic role to disease.

    Evidence Mouse knockout genetics with AML phenotyping, flow cytometry, RT-PCR, and histone modification analysis

    PMID:18728284

    Open questions at the time
    • Direct promoter binding at Hox/FoxP3 loci not shown
    • Whether increased H3K4/H3K9/H4K20me3 is cause or consequence of transformation unresolved
  4. 2012 High

    Identified ARID4B as a metastasis-promoting factor that interacts with BRMS1 and HDAC complex members, linking it to corepressor machinery and tumor progression.

    Evidence Co-IP with BRMS1/mSIN3A/mSDS3, shRNA knockdown, in vivo metastasis assays, and gene expression profiling of the Tpx2 network

    PMID:22693453

    Open questions at the time
    • Allele-dependent differential binding to mSIN3A/mSDS3 mechanistically unexplained
    • Direct ARID4B regulation of Tpx2 network genes not demonstrated by ChIP
  5. 2013 High

    Established ARID4A/ARID4B as transcriptional coactivators for AR and RB and demonstrated their requirement for male fertility and blood-testis barrier integrity.

    Evidence Co-IP of ARID4A-ARID4B, compound mouse knockouts, BTB permeability assays, and gene expression analysis

    PMID:23487765

    Open questions at the time
    • Direct coactivation mechanism at AR/RB target promoters not dissected here
    • Relative contributions of AR versus RB pathways to the testis phenotype not separated
  6. 2013 Medium

    Showed Arid4b is a direct microRNA target whose repression by miR-290-3p suppresses breast tumor growth and metastasis, defining post-transcriptional control of its oncogenic activity.

    Evidence Luciferase 3'UTR reporter assay, miRNA microarray, and in vivo tumor/metastasis assays

    PMID:23447578

    Open questions at the time
    • Whether ER pathway effects are direct ARID4B targets or secondary not resolved
    • Single lab
  7. 2015 High

    Pinpointed ARID4B as an AR coactivator required cell-autonomously in Sertoli cells for spermatogenesis, identifying Rhox5 as a direct functional AR target.

    Evidence Sertoli cell-specific Cre-lox knockout, fertility testing, histology, and AR coactivation assays

    PMID:26258622

    Open questions at the time
    • Chromatin recruitment mechanism of ARID4B to AR target genes not defined
    • Full repertoire of AR targets requiring ARID4B not mapped
  8. 2017 High

    Extended the Sertoli-cell role of ARID4B to spermatogonial stem cell niche establishment, identifying the downstream effector genes controlling that niche.

    Evidence Sertoli cell-specific knockout with gonocyte distribution/apoptosis analysis and transcriptomic profiling

    PMID:28207192

    Open questions at the time
    • Direct vs indirect regulation of GDNF/KITL/AMH/CYP26B1 by ARID4B not established
    • Mechanism linking ARID4B loss to basement-membrane detachment unknown
  9. 2019 High

    Defined a PTEN-ARID4B-PI3K axis in which ARID4B directly activates PI3K subunit genes by competing with histone H1 at their promoters, placing ARID4B as a chromatin-level driver of PI3K/AKT signaling.

    Evidence ChIP at PIK3CA/PIK3R2 promoters, knockdown/overexpression, in vivo prostate tumorigenesis, and patient signature analysis

    PMID:31551414

    Open questions at the time
    • Mechanism of PTEN-mediated suppression of ARID4B expression not detailed
    • How ARID4B displaces H1 to alter condensation not structurally defined
  10. 2020 High

    Showed ARID4B controls ESC differentiation through HDAC1-specific SIN3A subcomplexes that govern the H3K27ac/H3K27me3 balance at developmental loci.

    Evidence Pooled epigenetic shRNA screen, Co-IP of ARID4B-HDAC1, mESC differentiation assays, and ChIP-seq for H3K27me3/H3K27Ac

    PMID:33454011

    Open questions at the time
    • Basis for HDAC1 versus HDAC2 selectivity within SIN3A not resolved
    • Whether ARID4B targets developmental loci directly or via complex recruitment unclear
  11. 2021 High

    Demonstrated ARID4B directly binds the mTOR promoter to deposit activating H3K27ac, completing a PI3K-ARID4B-mTOR signaling pathway in muscle cells responsive to taurine.

    Evidence ChIP-PCR/qPCR, siRNA knockdown, CRISPR/dCas9 activation, and Western blots in C2C12 myoblasts

    PMID:34881695

    Open questions at the time
    • Coupling between upstream PI3K signaling and ARID4B promoter recruitment not defined
    • Generalizability of mTOR promoter regulation beyond myoblasts not tested
  12. 2021 Medium

    Linked ARID4B to PI3K/AKT signaling and cell-cycle/HDAC1 control in glioma, reinforcing its pro-tumorigenic signaling role in a second tumor type.

    Evidence shRNA knockdown in glioma cells with Western blot, cell-cycle flow cytometry, and migration/invasion assays

    PMID:33732001

    Open questions at the time
    • Direct promoter targets in glioma not identified by ChIP
    • The increase in HDAC1 upon ARID4B knockdown is mechanistically unexplained

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ARID4B is recruited to specific promoters and switches between coactivator (H3K27ac deposition, H1 displacement) and corepressor (SIN3A/HDAC1, H3K27me3) modes in a context-dependent manner remains unresolved.
  • No structural model of ARID4B-chromatin or ARID4B-complex interactions
  • Determinants of promoter selectivity unknown
  • Mechanism toggling activating vs repressive chromatin output undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0003677 DNA binding 3 GO:0042393 histone binding 2
Localization
GO:0005634 nucleus 3 GO:0005694 chromosome 3
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-1474165 Reproduction 3 R-HSA-162582 Signal Transduction 3 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
ARARID4ABRMS1H1HDAC1RB1SDS3SIN3A
Complex memberships
SIN3A complex

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 RBP1L1/ARID4B encodes a 1226-amino acid protein sharing 37% amino acid identity with retinoblastoma-binding protein 1 (RBP1/ARID4A); the protein localizes to the cytoplasm of MCF-7 breast cancer cells, as determined by immunoperoxidase staining with purified RBP1L1-specific IgG. cDNA library screening, Western blot, immunoperoxidase staining Journal of the National Cancer Institute Medium 11481388
2004 BRCAA1/ARID4B protein contains a novel antigen epitope (SSKKQKRSHK) at residues 610–619 and localizes to the cytoplasm of MCF-7 cells; the protein shares 37% identity with RBP1 and 74% with a partial RBP1 sequence, and its expression is associated with ER/PR status in breast cancer. Peptide synthesis, competitive inhibition ELISA, immunohistochemistry, Western blot Cancer epidemiology, biomarkers & prevention Medium 15247124
2006 ARID4B (Rbbp1l1/Arid4b) physically interacts with ARID4A (Rbbp1/Arid4a) and with the Snrpn promoter, forming part of an epigenetic complex. Combined homozygous deficiency of Arid4a and heterozygous deficiency of Arid4b in mice reduced trimethylation of histone H4K20 and H3K9 and reduced DNA methylation at the PWS-IC, shifting the maternal allele toward a paternal epigenotype. Mutations of Arid4b (or Arid4a, or Rb) suppressed an Angelman syndrome imprinting defect caused by a mutation at the AS-IC. Gene trap mutagenesis, co-immunoprecipitation (inferred from protein complex membership), chromatin immunoprecipitation, mouse knockout genetics, Western blot for histone modifications, bisulfite sequencing Genes & development High 17043311
2008 Arid4b haploinsufficiency combined with Arid4a deficiency in mice accelerates progression to acute myeloid leukemia (AML); Arid4a/Arid4b deficiency decreases expression of Hox genes (Hoxb3, Hoxb5, Hoxb6, Hoxb8) and FoxP3 in bone marrow, and increases histone trimethylation of H3K4, H3K9, and H4K20, identifying Arid4a and Arid4b as leukemia suppressor genes that regulate hematopoietic gene expression through histone modification. Mouse knockout genetics, complete blood counts, flow cytometry, histology, RT-PCR, Western blot, immunofluorescence for histone modifications Journal of the National Cancer Institute High 18728284
2012 ARID4B physically interacts with the breast cancer metastasis suppressor BRMS1, and also differentially binds to histone deacetylase complex members mSIN3A and mSDS3 depending on allelic variant. Ectopic expression of Arid4b promotes primary tumor growth and increases migration and invasion in vitro; shRNA knockdown reduces pulmonary metastases. Downregulation of the Tpx2 gene network (cell cycle and mitotic spindle regulators) accompanies loss of metastatic efficiency in Arid4b knockdown cells. Co-immunoprecipitation, shRNA knockdown, in vivo tumor/metastasis assays, in vitro migration/invasion assays, gene expression profiling PLoS genetics High 22693453
2013 ARID4A and ARID4B physically interact with each other; ARID4A is an RB-binding protein. In Arid4a−/−Arid4b+/− mice, combined deficiency causes progressive loss of male fertility with hypogonadism, spermatogenic arrest, and impaired blood-testis barrier integrity — phenotypes that recapitulate Sertoli cell-specific AR knockout and RB knockout mice. ARID4A and ARID4B were identified as transcriptional coactivators for androgen receptor (AR) and RB, with several AR- and RB-responsive genes identified as downstream targets. Co-immunoprecipitation (ARID4A–ARID4B interaction), mouse knockout genetics, histology, blood-testis barrier permeability assay, gene expression analysis 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, as confirmed by luciferase reporter assay; miR-290 upregulation suppresses both primary breast tumor growth and metastasis, and this effect is mediated through repression of Arid4b. Pathway analysis identified estrogen receptor (ER) signaling as a top canonical pathway affected by miR-290 upregulation. miRNA microarray, luciferase reporter assay, in vivo tumor/metastasis assays, pathway analysis Cancer research Medium 23447578
2015 ARID4B is required in Sertoli cells for spermatogenesis; Sertoli cell-specific Arid4b knockout (Arid4bSCKO) mice are completely infertile, showing impaired testis development, loss of germ cells, Sertoli cell-only phenotype, and delayed Sertoli cell maturation with spermatogenic arrest at the round spermatid stage. ARID4B functions as a coactivator of the androgen receptor (AR) and is required for optimal transcriptional activation of reproductive homeobox 5 (Rhox5), an AR target gene in Sertoli cells. Sertoli cell-specific Cre-lox knockout, histology, fertility testing, RT-PCR/gene expression analysis, androgen receptor coactivation assay Molecular endocrinology High 26258622
2017 In Sertoli cell-specific Arid4b knockout mice, ARID4B ablation causes abnormal detachment of Sertoli cells from the basement membrane during the gonocyte-to-SSC transition, preventing niche establishment for spermatogonial stem cell (SSC) formation. Gene expression profiling identified downstream effectors of ARID4B including gap junction protein alpha-1, KIT ligand, anti-Müllerian hormone, GDNF, inhibin alpha/beta, and CYP26B1 as genes governing SSC niche function. Sertoli cell-specific Arid4b knockout, histology, gene expression profiling, gonocyte distribution and apoptosis analysis Stem cells High 28207192
2018 miR-519b-3p directly binds the 3' UTR of ARID4B mRNA (validated by luciferase assay), and miR-519b-3p overexpression enhances responsiveness to chemoradiation in rectal cancer cells in an ARID4B-dependent manner. Luciferase reporter assay, miRNA overexpression, in vitro chemoradiation response assays Gene Medium 29477868
2019 PTEN suppresses ARID4B expression, while ARID4B acts as a transcriptional activator of PI3K subunit genes PIK3CA and PIK3R2, which are crucial for PI3K/AKT pathway activation. Reciprocal binding of ARID4B and histone H1 to the PIK3CA and PIK3R2 promoters modulates chromatin condensation. ARID4B is required for prostate tumorigenesis when PTEN is deficient, establishing a PTEN-ARID4B-PI3K axis. Chromatin immunoprecipitation (ChIP), promoter binding assays, gene knockdown/overexpression, in vitro and in vivo tumorigenesis assays, patient gene signature analysis Nature communications High 31551414
2020 ARID4B is critical for mouse embryonic stem cell (mESC) differentiation toward mesodermal and endodermal lineages; Arid4b-deficient mESCs have normal pluripotency but fail to upregulate meso/endodermal gene expression programs. ARID4B physically and functionally interacts with HDAC1 (but not HDAC2) within the SIN3A complex, suggesting functionally distinct SIN3A subcomplexes. ARID4B deficiency leads to increased H3K27me3 and reduced H3K27Ac at key developmental gene loci. Pooled epigenetic shRNA screen, co-immunoprecipitation (ARID4B–HDAC1 interaction), mESC differentiation assays, ChIP-seq for H3K27me3 and H3K27Ac, gene expression analysis The Journal of biological chemistry High 33454011
2020 Circ-SMARCA5 sponges miR-93-3p (also described as miR-39-3p in the abstract), and ARID4B is a direct target of this miRNA; circ-SMARCA5 upregulates ARID4B expression by sponging the miRNA, thereby inhibiting colorectal cancer cell proliferation, migration, and invasion. The miRNA–ARID4B interaction was validated by luciferase reporter assay. qRT-PCR, luciferase reporter assay, CCK-8 proliferation assay, wound healing assay, Transwell invasion assay, xenograft model Digestive and liver disease Low 32807692
2021 ARID4B knockdown in human glioma cells suppresses PI3K/AKT signaling (decreased p-mTOR, p-PI3K, p-AKT), induces G1 phase arrest via downregulation of Cyclin D1, increases HDAC1 expression leading to elevated acetyl-p53 and acetyl-H3, and reduces cell migration and invasion. shRNA knockdown via lentivirus, Western blot, flow cytometry (cell cycle), proliferation assay, migration/invasion assay OncoTargets and therapy Medium 33732001
2021 Taurine promotes ARID4B expression in a PI3K-dependent manner in C2C12 myoblasts. ARID4B directly binds the mTOR gene promoter (at the −4368 to −4591 bp site), and this binding is associated with H3K27ac (but not H3K27me3) at that site. ARID4B knockdown abolishes taurine-stimulated mTOR expression and phosphorylation, cell proliferation, and protein synthesis, whereas ARID4B gene activation (CRISPR/dCas9) has stimulatory effects, establishing a PI3K–ARID4B–mTOR pathway in muscle cells. ChIP-PCR, ChIP-qPCR, siRNA knockdown, CRISPR/dCas9 gene activation, Western blot, cell proliferation assay The British journal of nutrition High 34881695
2018 ARID4B expression correlates with WHO grade in gliomas and meningiomas; in vitro ARID4B protein is elevated in some glioma cell lines relative to normal brain tissue (Western blot), establishing overexpression as a feature of malignant primary brain tumors. Western blot (cell lines), immunohistochemistry (tissue microarray), GEO dataset analysis Journal of clinical pathology Low 27451434

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 333 28514443
2010 Adipose tissue branched chain amino acid (BCAA) metabolism modulates circulating BCAA levels. The Journal of biological chemistry 319 20093359
2018 The BCKDH Kinase and Phosphatase Integrate BCAA and Lipid Metabolism via Regulation of ATP-Citrate Lyase. Cell metabolism 291 29779826
2019 Targeting BCAA Catabolism to Treat Obesity-Associated Insulin Resistance. Diabetes 270 31167878
2004 Exercise promotes BCAA catabolism: effects of BCAA supplementation on skeletal muscle during exercise. The Journal of nutrition 263 15173434
2019 Loss of BCAA Catabolism during Carcinogenesis Enhances mTORC1 Activity and Promotes Tumor Development and Progression. Cell metabolism 254 30661928
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 211 35931683
2020 BCAT2-mediated BCAA catabolism is critical for development of pancreatic ductal adenocarcinoma. Nature cell biology 204 32029896
2007 BCAA-enriched snack improves nutritional state of cirrhosis. Nutrition (Burbank, Los Angeles County, Calif.) 163 17234504
2019 Loss of EZH2 Reprograms BCAA Metabolism to Drive Leukemic Transformation. Cancer discovery 150 31189531
2023 METTL16 drives leukemogenesis and leukemia stem cell self-renewal by reprogramming BCAA metabolism. Cell stem cell 141 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 121 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 95 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
2024 The role of BCAA metabolism in metabolic health and disease. Experimental & molecular medicine 80 38956299
2008 Identification of chromatin remodeling genes Arid4a and Arid4b as leukemia suppressor genes. Journal of the National Cancer Institute 75 18728284
2024 BCAA-nitrogen flux in brown fat controls metabolic health independent of thermogenesis. Cell 74 38653240
2022 A randomized placebo-controlled clinical trial for pharmacological activation of BCAA catabolism in patients with type 2 diabetes. Nature communications 71 35717342
2023 Enhanced BCAT1 activity and BCAA metabolism promotes RhoC activity in cancer progression. Nature metabolism 70 37337119
2020 Muscle-Liver Trafficking of BCAA-Derived Nitrogen Underlies Obesity-Related Glycine Depletion. Cell reports 69 33176135
2024 BCAA-producing Clostridium symbiosum promotes colorectal tumorigenesis through the modulation of host cholesterol metabolism. Cell host & microbe 65 39106870
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 64 32238881
2017 Krüppel-like factor 15: Regulator of BCAA metabolism and circadian protein rhythmicity. Pharmacological research 61 29288718
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 60 23487765
2001 BCAA intake affects protein metabolism in muscle after but not during exercise in humans. American journal of physiology. Endocrinology and metabolism 60 11440914
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 54 35701874
2023 Branched-chain amino acid catabolism in muscle affects systemic BCAA levels but not insulin resistance. Nature metabolism 53 37100997
2019 Associations Between Dietary Protein Sources, Plasma BCAA and Short-Chain Acylcarnitine Levels in Adults. Nutrients 53 30650556
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 51 30263672
2018 Dietary Pattern and Plasma BCAA-Variations in Healthy Men and Women-Results from the KarMeN Study. Nutrients 49 29762522
2023 BCAA insufficiency leads to premature ovarian insufficiency via ceramide-induced elevation of ROS. EMBO molecular medicine 46 36847712
2016 BCAA Metabolism and NH3 Homeostasis. Advances in neurobiology 46 27885628
2019 BCAA Catabolic Defect Alters Glucose Metabolism in Lean Mice. Frontiers in physiology 45 31551816
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
2019 Identification of the PTEN-ARID4B-PI3K pathway reveals the dependency on ARID4B by PTEN-deficient prostate cancer. Nature communications 40 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
2024 BCAA mediated microbiota-liver-heart crosstalk regulates diabetic cardiomyopathy via FGF21. Microbiome 37 39182099
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
2023 Targeting BCAA metabolism to potentiate metformin's therapeutic efficacy in the treatment of diabetes in mice. Diabetologia 34 37581618
2023 Impaired BCAA catabolism in adipose tissues promotes age-associated metabolic derangement. Nature aging 32 37488415
2022 Elevated BCAA Suppresses the Development and Metastasis of Breast Cancer. Frontiers in oncology 31 35785192
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
2018 BCAT1 promotes proliferation of endometrial cancer cells through reprogrammed BCAA metabolism. International journal of clinical and experimental pathology 30 31949641
2024 CPT1A loss disrupts BCAA metabolism to confer therapeutic vulnerability in TP53-mutated liver cancer. Cancer letters 29 38823763
2021 Metabolic flexibility via mitochondrial BCAA carrier SLC25A44 is required for optimal fever. eLife 29 33944778
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 28 34004356
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 28 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
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.) 26 38049750
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 25 33800577
2023 Disrupted cardiac fibroblast BCAA catabolism contributes to diabetic cardiomyopathy via a periostin/NAP1L2/SIRT3 axis. Cellular & molecular biology letters 24 37993768
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
2019 Effect of metformin on myotube BCAA catabolism. Journal of cellular biochemistry 23 31385363
2020 Excessive BCAA regulates fat metabolism partially through the modification of m6A RNA methylation in weanling piglets. Nutrition & metabolism 22 31998401
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
2024 BCAA metabolism in pancreatic cancer affects lipid balance by regulating fatty acid import into mitochondria. Cancer & metabolism 21 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.) 20 34525937
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
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 19 36844730
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
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 18 39490614
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 18 35334826
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
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
2021 AICAR stimulates mitochondrial biogenesis and BCAA catabolic enzyme expression in C2C12 myotubes. Biochimie 16 34798200
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
2023 Convergent genomic diversity and novel BCAA metabolism in intrahepatic cholangiocarcinoma. British journal of cancer 15 37076565
2021 Gentamicin Induced Microbiome Adaptations Associate With Increased BCAA Levels and Enhance Severity of Influenza Infection. Frontiers in immunology 15 33708192
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
2013 Characterization of BcaA, a putative classical autotransporter protein in Burkholderia pseudomallei. Infection and immunity 15 23340315
2004 Administration of granulated BCAA and quality of life. Hepatology research : the official journal of the Japan Society of Hepatology 15 15607138
2021 Taurine stimulates protein synthesis and proliferation of C2C12 myoblast cells through the PI3K-ARID4B-mTOR pathway. The British journal of nutrition 14 34881695
2004 Nocturnal energy and BCAA supplementation in patients with liver cirrhosis. Hepatology research : the official journal of the Japan Society of Hepatology 14 15607141
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
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
2023 Empowering frail older adults: multicomponent elastic-band exercises and BCAA supplementation unleash physical health and preserve haematological biomarkers. Frontiers in sports and active living 12 37720080
2022 Evaluation of therapeutic strategies targeting BCAA catabolism using a systems pharmacology model. Frontiers in pharmacology 12 36518669

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