Affinage

BCAT1

Branched-chain-amino-acid aminotransferase, cytosolic · UniProt P54687

Length
386 aa
Mass
43.0 kDa
Annotated
2026-04-28
100 papers in source corpus 36 papers cited in narrative 36 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BCAT1 is the cytosolic branched-chain amino acid transaminase that reversibly transfers α-amino groups from leucine, isoleucine, and valine to α-ketoglutarate, generating glutamate and branched-chain α-keto acids (BCKAs), thereby coupling BCAA catabolism to α-KG availability, mTORC1 signaling, and epigenetic regulation. By consuming α-KG, BCAT1 restricts the activity of α-KG-dependent dioxygenases including TET2 and histone demethylases, driving DNA and histone hypermethylation that phenocopies IDH mutations in AML and glioma (PMID:29144447, PMID:38340163); its BCKA products directly activate RhoC GTPase to promote cell motility (PMID:37337119) and sustain oxidative phosphorylation and nucleotide biosynthesis required for proliferation (PMID:35499760). Independent of its transaminase activity, BCAT1 possesses a CXXC redox motif that confers antioxidant H₂O₂-metabolizing capacity and localizes to mitotic structures to regulate Aurora B kinase centromere targeting, ensuring accurate chromosome segregation (PMID:36260995, PMID:35453368). BCAT1 protein stability is controlled by BCKDK-mediated phosphorylation that antagonizes STUB1/CHIP E3 ubiquitin ligase-dependent K48-linked ubiquitination and proteasomal degradation, a process counteracted by SIRT5 desuccinylation at K39 (PMID:38621458, PMID:39075053, PMID:40195331).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1999 Medium

    The earliest functional evidence showed that BCAT1 enzymatic products — specifically the branched-chain keto acid α-ketoisocaproate — have direct biological activity, capable of inducing apoptosis, establishing that BCAT1's downstream metabolites are not inert intermediates.

    Evidence BCAT1 overexpression and α-ketoisocaproate supplementation in murine cells under serum deprivation

    PMID:10471790

    Open questions at the time
    • Single lab, not independently replicated
    • Mechanism of BCKA-induced apoptosis not defined
    • Physiological relevance of overexpression-level metabolite flux unclear
  2. 2004 Medium

    BCAT1 was found to be neuron-specific in the adult brain with differential subcellular localization in glutamatergic versus GABAergic neurons, suggesting a role in neurotransmitter precursor supply.

    Evidence Immunohistochemistry in rat brain with cell-type resolution

    PMID:15329886

    Open questions at the time
    • Descriptive localization only; no functional perturbation in neurons
    • Whether BCAT1 controls neurotransmitter pools was not tested
    • Human relevance not demonstrated
  3. 2013 High

    Two studies established BCAT1 as both a critical metabolic dependency in glioblastoma (through glutamate production and proliferation support) and a direct transcriptional target of c-Myc, linking oncogene activation to BCAA catabolism.

    Evidence shRNA knockdown in glioma cells with xenograft validation; ChIP and luciferase reporter assays for c-Myc binding to BCAT1 promoter in nasopharyngeal carcinoma

    PMID:23758864 PMID:23793099

    Open questions at the time
    • Whether c-Myc regulation of BCAT1 is universal across cancer types
    • Identity of downstream metabolic effectors beyond glutamate not resolved
  4. 2014 High

    Using knockout mice, BCAT1 was shown to control intracellular leucine levels in CD4+ T cells downstream of TCR/calcineurin-NFAT signaling, with BCAT1 loss causing aberrantly elevated mTORC1 activity, revealing BCAT1 as a metabolic rheostat for immune cell activation.

    Evidence BCATc knockout mouse T cells; mTORC1 substrate phosphorylation; glycolysis measurement

    PMID:24847056

    Open questions at the time
    • Whether BCAT1's mTORC1-modulating role is mediated by leucine depletion versus BCKA production
    • Effects on T cell differentiation and in vivo immune responses not fully characterized
  5. 2017 High

    A pivotal mechanistic advance showed that BCAT1 controls α-KG availability in AML, directly linking its transaminase activity to epigenetic reprogramming: BCAT1 overexpression depleted α-KG, impaired TET2 dioxygenase activity, and caused DNA hypermethylation phenocopying IDH mutations.

    Evidence BCAT1 knockdown/overexpression in AML cells with metabolomics, DNA methylation profiling, and HIF1α degradation measurement

    PMID:29144447

    Open questions at the time
    • Whether BCAT1's epigenetic effects are sufficient for leukemic transformation alone
    • Relative contributions of TET2 versus EGLN1/HIF1α pathways downstream of α-KG depletion
  6. 2020 High

    The metabolic crosstalk axis was expanded to the tumor microenvironment when BCAT1 in cancer-associated fibroblasts was shown to be regulated by TGF-β/SMAD5 signaling, producing BCKAs that are secreted to fuel pancreatic cancer cell metabolism.

    Evidence TGF-β/SMAD5 manipulation in CAFs; isotope tracing of BCAA metabolism; patient-derived material validation

    PMID:32694827

    Open questions at the time
    • Whether BCKA transfer from CAFs to cancer cells involves specific transporters
    • Quantitative contribution of CAF-derived BCKAs versus cancer cell-autonomous BCAA catabolism
  7. 2022 High

    A non-metabolic moonlighting function was discovered: BCAT1 localizes to mitotic structures and its CXXC redox motif controls Aurora B kinase centromere localization and chromosome segregation accuracy, independent of its transaminase activity. Separately, the CXXC motif was shown to directly metabolize H₂O₂, conferring intrinsic antioxidant activity.

    Evidence CXXC motif mutagenesis with rescue in cancer cells and iPSCs; purified recombinant BCAT1 H₂O₂ metabolism assay; live-cell imaging and chromosome segregation assays

    PMID:35453368 PMID:36260995

    Open questions at the time
    • Structural basis for how CXXC sulfenylation recruits Aurora B
    • Whether the antioxidant function and mitotic function are mechanistically coupled
    • Relative contribution of redox versus metabolic functions to tumor growth
  8. 2022 High

    BCKA products of BCAT1 were established as the critical downstream effectors in GBM, rescuing oxidative phosphorylation, mTORC1 activity, and nucleotide biosynthesis after BCAT1 loss, resolving the question of whether α-KG depletion or BCKA generation is the dominant output.

    Evidence BCAT1 KO with BCKA supplementation rescue in patient-derived GBM models; metabolic measurements including NAD+/NADH and nucleotides

    PMID:35499760

    Open questions at the time
    • Molecular targets of BCKAs that restore mTORC1 and nucleotide synthesis
    • Whether BCKAs act through allosteric effects, as metabolic fuels, or as signaling molecules
  9. 2023 High

    The signaling mechanism of BCAT1-derived BCKAs was partly resolved: BCAT1 directly interacts with RhoC GTPase, and BCKAs bind RhoC to activate its GTPase activity, providing a direct metabolite-to-signaling link driving cell motility and metastasis.

    Evidence Co-IP of BCAT1-RhoC; biochemical BCKA-RhoC binding assay; gain-of-function BCAT1-E61A mutant; in vivo metastasis model

    PMID:37337119

    Open questions at the time
    • Structural basis of BCKA-RhoC binding
    • Whether BCKA-RhoC activation occurs in non-cancer contexts
    • Specificity for RhoC versus other Rho family GTPases
  10. 2024 High

    The post-translational regulation of BCAT1 was delineated: BCKDK phosphorylates BCAT1 at S5/S9/T312 to enhance activity and stability; STUB1/CHIP ubiquitinates BCAT1 at K48/K360 for proteasomal degradation; and BCKDK also phosphorylates STUB1-S19 to disrupt its interaction with BCAT1, creating a coherent stabilization circuit.

    Evidence Mass spectrometry phosphosite mapping; Co-IP; ubiquitination and in vitro kinase assays; domain mapping of CHIP-BCAT1 interaction; glioma models

    PMID:38621458 PMID:39075053

    Open questions at the time
    • Phosphatases that reverse BCKDK-mediated phosphorylation
    • Whether BCKDK regulation of BCAT1 is tissue-specific
    • Crystal structure of BCAT1-CHIP complex
  11. 2025 High

    SIRT5 was identified as a desuccinylase stabilizing BCAT1 by removing succinylation at K39, which otherwise promotes CHIP-mediated ubiquitination; separately, NOTCH1 and NR4A1 were identified as direct transcriptional regulators of BCAT1 in T-ALL and macrophages respectively, expanding the transcription factor repertoire controlling BCAT1.

    Evidence SIRT5-BCAT1 interaction by proteomics and Co-IP with succinylation site mapping; NOTCH1 ChIP at BCAT1 promoter with genetic KO; NR4A1 KO mouse atherosclerosis model

    PMID:39234857 PMID:39985585 PMID:40195331

    Open questions at the time
    • Succinylation writer enzyme for BCAT1-K39 unknown
    • Whether SIRT5-BCAT1 axis operates beyond glioma
    • Full promoter architecture integrating c-Myc, NOTCH1, STAT3, NR4A1, TFEB inputs

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis for BCAT1's CXXC-mediated mitotic and antioxidant functions, how BCKA metabolites allosterically activate diverse targets (RhoC, mTORC1), whether the metabolic and redox moonlighting functions are coordinately regulated in vivo, and the physiological significance of BCAT1 in neuronal BCAA metabolism and neurotransmitter production.
  • No crystal structure of BCAT1 in complex with mitotic or signaling partners
  • No reconstituted system demonstrating BCKA direct activation of mTORC1
  • Neuron-specific BCAT1 knockout phenotype not reported

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 5 GO:0016209 antioxidant activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005829 cytosol 3 GO:0005694 chromosome 1
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-162582 Signal Transduction 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-4839726 Chromatin organization 2 R-HSA-9612973 Autophagy 2 R-HSA-1640170 Cell Cycle 1
Partners
AURBBCKDKIRE1RHOCSIRT5STUB1

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 BCAT1 initiates BCAA catabolism in glioblastoma cells; suppression of BCAT1 blocked glutamate excretion, reduced proliferation and invasiveness in vitro, and decreased tumor growth in xenograft models, establishing BCAT1 as required for glioma cell proliferation through amino acid catabolism. shRNA knockdown in glioma cell lines + xenograft model; metabolite measurements (glutamate excretion); ectopic mutant IDH1 overexpression suppressing BCAT1 Nature medicine High 23793099
2013 c-Myc directly binds the BCAT1 promoter and transcriptionally upregulates BCAT1 expression in nasopharyngeal carcinoma cells, as demonstrated by ChIP and luciferase reporter assays. ChIP assay; luciferase reporter assay; c-Myc siRNA knockdown reducing BCAT1 expression Molecular cancer High 23758864
2017 BCAT1 transfers α-amino groups from BCAAs to α-ketoglutarate (αKG), thereby restricting intracellular αKG levels in AML stem cells; BCAT1 knockdown caused αKG accumulation leading to EGLN1-mediated HIF1α degradation; BCAT1 overexpression decreased αKG and caused TET2-dependent DNA hypermethylation, mimicking IDH mutation effects. BCAT1 knockdown/overexpression in AML cells; metabolomics (intracellular αKG measurement); proteomic analysis; DNA methylation profiling; HIF1α protein level measurement Nature High 29144447
2014 BCATc (BCAT1) expression is induced by T cell receptor (TCR) signaling via the calcineurin-NFAT pathway in CD4+ T cells; BCATc controls intracellular leucine levels, and its absence increases mTORC1 activation (elevated S6 and 4EBP-1 phosphorylation) and glycolytic metabolism. BCATc knockout mouse; cyclosporin A (calcineurin-NFAT inhibitor) treatment; leucine transamination assay; mTORC1 substrate phosphorylation (immunoblot); glycolysis measurement (Seahorse) The Journal of biological chemistry High 24847056
2004 BCATc (BCAT1) is exclusively expressed in neurons (not astrocytes) in the adult rat brain; in glutamatergic neurons it localizes to axons and nerve terminals, while in GABAergic neurons it concentrates in cell bodies, suggesting a role in regulating glutamate available for neurotransmitter release or GABA synthesis. Immunohistochemistry in rat brain; cell-type-specific localization in cerebellum and hippocampus The Journal of comparative neurology Medium 15329886
1999 Overexpression of BCAT1/ECA39 in murine cells promotes apoptosis under serum deprivation; the branched-chain keto acid α-ketoisocaproate (product of leucine catabolism by BCAT1) can independently induce rapid apoptotic cell death, suggesting the apoptotic effect is mediated by BCAA-derived keto acid metabolites. Overexpression of BCAT1 in murine cells; serum deprivation assay; α-ketoisocaproate treatment; cell viability/apoptosis assays FEBS letters Medium 10471790
2017 BCAT1 promotes breast cancer cell growth by activating mTOR signaling, enhancing mitochondrial biogenesis and ATP production, and suppressing mitochondrial ROS; this effect is specific to mTOR (not AMPK or SIRT1). BCAT1 knockdown/overexpression in breast cancer cells; mTOR pathway inhibitor; colony formation; mitochondrial biogenesis and ATP production assays Biochemical and biophysical research communications Medium 28235484
2020 In pancreatic ductal adenocarcinoma, TGF-β signaling via the SMAD5 axis directly targets BCAT1 in cancer-associated fibroblasts (CAFs), dictating internalization of extracellular matrix to supply amino acid precursors for branched-chain α-ketoacid (BCKA) secretion by CAFs that fuels PDAC cancer cells. TGF-β/SMAD5 pathway manipulation in CAFs; isotope tracing of BCAA metabolism; BCAT1 knockdown in CAFs; CTC and PDAC tissue slice validation Nature metabolism High 32694827
2022 BCAT1 localizes to mitotic structures and has a non-metabolic moonlighting function as a mitotic regulator; its CXXC redox motif controls cysteine sulfenylation in mitotic cells, promoting Aurora kinase B localization to centromeres and securing accurate chromosome segregation. Gene knockout and rescue strategies in cancer cells and iPSCs; live cell imaging of BCAT1 at mitotic structures; CXXC motif mutagenesis; Aurora B localization by immunofluorescence; chromosome segregation assays; cerebral organoid and mouse syngraft tumor growth models Cell reports High 36260995
2022 The BCAT1 CXXC motif has antioxidant activity: purified wild-type BCAT1 protein can metabolize H2O2 in vitro, whereas CXXC motif mutant BCAT1 or wild-type BCAT2 cannot; this activity buffers intracellular ROS in AML cells and reduces myeloid differentiation markers. In vitro H2O2 metabolism assay with purified recombinant BCAT1 wild-type vs. CXXS mutant; intracellular ROS measurement in U937 AML cells overexpressing WT vs. CXXS BCAT1; myeloid differentiation markers (CD11b, CD14, CD68, CD36) Antioxidants (Basel, Switzerland) High 35453368
2022 Loss of BCAT1 in IDH-wildtype GBM cells increases NAD+/NADH ratio but impairs oxidative phosphorylation, mTORC1 activity, and nucleotide biosynthesis; supplementation with branched-chain α-ketoacids (BCKA, downstream products of BCAT1) rescues these defects and prevents cell death, establishing BCAT1-generated BCKAs as the critical downstream mediators. BCAT1 inhibitor (gabapentin) + αKG co-treatment synthetic lethality screen; BCAT1 KO + BCKA supplementation rescue; patient-derived GBM in vitro and in vivo models; metabolic measurements (NAD+/NADH, nucleotides, ATP, mTORC1 substrates) Cancer research High 35499760
2023 BCAT1 directly interacts with RhoC GTPase, elevating RhoC activity; additionally, BCAA-derived branched-chain α-keto acids (BCKAs) directly bind to RhoC and promote its GTPase activity, linking BCAT1 enzymatic activity to cell motility through RhoC activation. Co-immunoprecipitation of BCAT1-RhoC interaction; BCKA direct binding to RhoC (biochemical binding assay); BCAT1 gain-of-function mutation (E61A) with higher enzymatic activity; BCAT1 KO rescue with BCAT1-E61A or BCKA supplementation; in vivo peritoneal metastasis model; candesartan identified as BCAT1-E61A inhibitor Nature metabolism High 37337119
2021 BCAT1 increases cisplatin resistance in cancer cells by inducing mTOR-mediated autophagy via leucine metabolism; cisplatin upregulates BCAT1, which decreases leucine availability to suppress mTOR signaling and activate autophagy, thereby reducing cisplatin sensitivity. BCAT1 knockdown/overexpression; leucine and BCAA supplementation rescuing mTOR activity and autophagy; chloroquine (autophagy inhibitor) in vivo; mTOR substrate phosphorylation assays Cell death & disease Medium 33568627
2022 BCAT1 promotes osteoclast maturation through its enzymatic BCAA catabolism activity; enzymatically dead BCAT1 abrogated osteoclast maturation, and the specific BCAT1 inhibitor gabapentin reduced osteoclast differentiation and inhibited LPS-induced bone loss in mice. Expression of enzymatically dead BCAT1 mutant; gabapentin (BCAT1 inhibitor) treatment; in vitro RANKL-induced osteoclast differentiation assay; in vivo LPS-induced calvaria bone loss model Experimental & molecular medicine High 35760874
2024 BCKDK phosphorylates BCAT1 at S5, S9, and T312, increasing its catalytic and antioxidant activity and stability; STUB1 is an E3 ubiquitin ligase for BCAT1 that promotes K48-linked ubiquitin degradation of BCAT1; BCKDK phosphorylation of STUB1 at S19 disrupts its interaction with BCAT1, thereby inhibiting BCAT1 ubiquitination and degradation. Mass spectrometry identification of phosphorylation sites; co-immunoprecipitation of BCKDK-BCAT1 and STUB1-BCAT1; mutagenesis of phosphorylation sites; ubiquitination assay; in vitro kinase assay; in vivo xenograft model Cancer letters High 38621458
2024 CHIP (STUB1) E3 ubiquitin ligase interacts with BCAT1 via its coiled-coil domain, promoting K48-linked ubiquitination and proteasomal degradation of BCAT1 at K360; reduced CHIP expression leads to high BCAT1 in glioma cells, and CHIP-mediated BCAT1 degradation reduces glutathione synthesis, increases oxidative stress, and sensitizes glioma cells to temozolomide. Co-immunoprecipitation of CHIP-BCAT1; domain mapping (CC domain); ubiquitination site mutagenesis (K360); proteasome inhibitor treatment; GSH measurement; in vitro and in vivo glioma models Cell death & disease High 39075053
2025 SIRT5 desuccinylates BCAT1 at K39, preventing its interaction with the E3 ligase CHIP and thereby stabilizing BCAT1 protein against ubiquitin-proteasome degradation, leading to increased BCAA catabolism, ferroptosis resistance, and glioma cell proliferation. Proteomics/metabolomics identifying BCAT1 as SIRT5 substrate; succinylation site mapping at K39; co-immunoprecipitation of BCAT1-CHIP interaction; SIRT5 knockdown + BCAT1 overexpression rescue; in vitro and in vivo glioma models Cell death & disease High 40195331
2025 NOTCH1 directly controls BCAT1 expression by binding to the BCAT1 promoter; BCAT1 depletion in NOTCH1-driven T-ALL cells redirected leucine metabolism towards 3-hydroxy butyrate (3-HB) production (an endogenous HDAC inhibitor), altered protein acetylation levels, and sensitized cells to DNA damaging agents. NOTCH1 gain-of-function retroviral T-ALL model; Bcat1 genetic KO mouse cells; BCAT1 promoter binding by NOTCH1 (ChIP); leucine metabolite profiling; protein acetylation measurement; patient-derived xenograft models with etoposide combination treatment Haematologica High 39234857
2024 BCAT1 inhibition in CD4+ T cells blocks production of β-hydroxy β-methylbutyric acid (HMB) via cytosolic leucine catabolism through BCAT1 and HPD/HPDL; HMB upregulates HIF1α mRNA and activates the mTORC1-HIF1α pathway to drive IL-17 production; BCAT1 inhibition reduced EAE severity in vivo. BCAT1 shRNA knockdown; BCAT1 inhibitor treatment (Bi2, LβhL); HMB supplementation rescue; HIF1α mRNA/protein measurement; IL-17 production assay; EAE mouse model Experimental & molecular medicine High 39085353
2020 BCAT1 binds the RNA-binding protein ZNF423 via its mRNA 3'-UTR AU-rich elements; BCAT1 activates autophagy in hypoxic pulmonary artery smooth muscle cells by binding IRE1 on the ER membrane to activate the XBP-1-RIDD axis, leading to accumulation of BECN1 and Atg5. Co-immunoprecipitation of BCAT1-IRE1 interaction; ZNF423 RNA pull-down with BCAT1 3'-UTR; BCAT1 knockdown/overexpression; autophagy marker measurement (BECN1, Atg5); hypoxic PASMC model Cell death & disease Medium 32938905
2021 In lung cancer cells, BCAT1 overexpression depletes α-ketoglutarate and promotes expression of SOX2, a transcription factor for cancer cell stemness and metastasis, thereby promoting metastasis. Quantitative mass spectrometry; shRNA BCAT1 knockdown reducing metastasis in vitro and in vivo; αKG measurement; SOX2 expression analysis Theranostics Medium 34646394
2016 DOT1L histone methyltransferase regulates BCAT1 expression through H3K79 methylation; BCAT1 is required downstream of DOT1L for sphere formation and cell migration in breast cancer cells. DOT1L knockdown/overexpression; H3K79 methylation at BCAT1 locus; BCAT1 KD rescue of DOT1L effects; sphere formation and migration assays Biochimie Medium 26783998
2018 The lncRNA CRNDE acts as a competing endogenous RNA (ceRNA) to sponge miR-203, which directly targets the BCAT1 3'-UTR; CRNDE-mediated inhibition of miR-203 elevates BCAT1 expression and promotes HCC cell proliferation, invasion, and migration. Dual luciferase reporter assay confirming miR-203 targeting BCAT1 3'-UTR and CRNDE sponging miR-203; CRNDE/miR-203/BCAT1 expression correlation; xenograft model Journal of cellular physiology Medium 30230527
2019 DNMT1 hypermethylates the miR-124-3p promoter to silence miR-124-3p; miR-124-3p directly targets the BCAT1 mRNA 3'-UTR to suppress BCAT1 expression; DNMT1 knockdown reduces BCAT1 via miR-124-3p restoration in esophageal squamous cell carcinoma. miR-124-3p 3'-UTR targeting of BCAT1 (luciferase assay inferred); DNMT1 knockdown; miR-124-3p overexpression reducing BCAT1; proliferation/migration assays BMC cancer Medium 31226958
2024 BCAT1 promotes TNBC progression by maintaining leucine, isoleucine, and valine (BCAA) synthesis; BCAA-supported SHOC2 (a leucine-rich repeat protein) expression activates downstream RAS-ERK signaling; Eupalinolide B (EB) was identified as a direct BCAT1 inhibitor and inhibits SHOC2-RAS-ERK to induce TNBC cell apoptosis. ABPP technology + pull-down WB + CETSA-WB + MST identifying BCAT1 as direct EB target; HPLC metabolomics; proteomic sequencing; BCAT1 KO/OE with SHOC2-RAS-ERK pathway readout; in vivo mouse models Journal of advanced research High 39490614
2024 HuR RNA-binding protein directly binds BCAT1 mRNA and increases its stability and translation, thereby upregulating BCAT1 protein levels; elevated BCAT1 activates ERK5 signaling to promote castration-resistant prostate cancer progression. RNA immunoprecipitation (RIP) assay; mRNA half-life assay; HuR KO by Cas9; HuR inhibitor KH-3; ERK5 pathway measurement Journal of translational medicine Medium 38369471
2024 In AML cells, high BCAT1 expression limits intracellular αKG levels, which impairs αKG-dependent histone demethylase activity and upregulates H3K9me3; elevated H3K9me3 inhibits ATM expression and blocks DNA damage repair, sensitizing high-BCAT1 AML cells to PARP inhibitors. BCAT1 KO/OE AML cell lines; αKG measurement; H3K9me3 ChIP; ATM expression; PARP inhibitor sensitivity in vitro and in vivo Journal of molecular medicine Medium 38340163
2022 BCAT1 promotes leukemia development downstream of the P2X1-PBX3 signaling axis; ATP-P2X1 signaling upregulates PBX3 which transactivates BCAT1, and BCAT1 is required to maintain leukemia-initiating cell self-renewal. P2X1 deletion mouse AML model; PBX3-BCAT1 transactivation; BCAT1 knockdown in human AML cell lines; in vivo transplantation assays Leukemia Medium 36418376
2024 BCAA/BCAT1 signaling enhances CREB phosphorylation, which is required for maintenance of TKI-resistant CML cells; BCAT1 knockdown dramatically reduces proliferation of TKI-resistant human leukemia lines and abrogates leukemia in BCR-ABL-T315I murine CML model. BCAT1 knockdown in murine BCR-ABLT315I CML model + human TKI-resistant cell lines; BCAA stimulation; CREB phosphorylation measurement; in vivo transplantation Cellular oncology Medium 39412615
2025 BCAT1 activation in Müller cells under diabetic conditions reduces intracellular αKG, increases H3K4me3 at inflammatory gene (IL-6, TNF-α) promoters, and drives retinal inflammation; Plk4 kinase phosphorylates BCAT1 at threonine 333 to negatively regulate its activity. ChIP for H3K4me3 at inflammatory gene promoters; targeted metabolomics (αKG measurement); kinase screening identifying Plk4; BCAT1 inhibitor (BAY-069, ERG240) treatment in diabetic mouse models; Bcat1 single-cell expression mapping Investigative ophthalmology & visual science Medium 40530920
2024 Transcription factor EB (TFEB) transcriptionally regulates BCAT1 expression; TFEB knockdown inhibits BCAA catabolism in pancreatic cancer cells by blocking BCAT1, reducing cell proliferation and metastasis. TFEB knockdown; BCAT1 expression measurement; BCAA catabolism assays; proliferation and metastasis assays; BCAA deprivation + eltrombopag (TFEB inhibitor) combination Cell proliferation Medium 38938061
2025 NR4A1 nuclear receptor transcriptionally inhibits Bcat1 expression in macrophages; NR4A1 deficiency upregulates Bcat1, which activates the integrated stress response (ISR) in macrophages, promoting vulnerable atherosclerotic plaque formation. NR4A1 KO mouse (ApoE-/-;NR4A1-/-) vulnerable plaque model; Bcat1 identified as NR4A1 transcriptional target; Bcat1 inhibitor (ERG240) treatment; ISR pathway measurement Cellular and molecular life sciences Medium 39985585
2024 BCAT1 inhibition in trophoblasts blocks NF-κB pathway activation (reducing p-IκBα and nuclear NF-κB p65 translocation), suppresses NLRP3 inflammasome activation, reduces inflammatory cytokine release, and decreases trophoblast apoptosis in LPS-induced inflammation models. BCATc Inhibitor 2 treatment; EMSA for NF-κB DNA binding; p-IκBα and nuclear NF-κB p65 immunoblot/IF; TUNEL apoptosis assay; cytokine ELISA; LPS-induced mouse pregnancy loss model Cell and tissue research Medium 39356334
2023 BCAT1 controls embryonic neural stem cell (NSC) proliferation and differentiation; BCAT1 is specifically highly expressed in layer II/III and IV neurons, and shRNA-mediated BCAT1 suppression reduces NSC proliferation and causes abnormal development of these cortical layers. Single-cell RNA-seq trajectory analysis; shRNA knockdown of BCAT1 in NSCs; assessment of cortical layer neuron development in vivo Molecular brain Medium 37344908
2022 BCAT1 activity is required for ferroptosis protection in myocardial ischemia; BCAT1/BCAT2 overexpression activates the Keap1/Nrf2/HO-1 antioxidant pathway, and BCAT1 or BCAT2 siRNA knockdown promotes ferroptosis and decreases cell viability in cardiomyocytes. BCAT1/BCAT2 siRNA knockdown; cardiac-specific BCAT1/BCAT2 overexpression in MI mice; Keap1/Nrf2/HO-1 pathway measurement; ferroptosis markers (GPX4, ACSL4); metabolomics identifying BCAT1/BCAT2 as RUS targets Antioxidants (Basel, Switzerland) Medium 35326233
2024 BCAT1 expression is regulated by STAT3: mutant IDH1 inhibitor treatment decreases mutant IDH1-STAT3 binding, freeing STAT3 for phosphorylation at Tyr-705 (pSTAT3-Y705) and nuclear translocation, which transcriptionally increases BCAT1 levels; STAT3 knockdown or inhibition attenuates mutant IDH1 inhibitor-mediated BCAT1 upregulation. STAT3 knockdown; pharmacological STAT3 inhibition; pSTAT3-Y705 immunoblot; nuclear translocation assay; Co-immunoprecipitation of mutant IDH1-STAT3; BCAT1 expression measurement Biochimica et biophysica acta. Molecular cell research Medium 34329662

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 BCAT1 promotes cell proliferation through amino acid catabolism in gliomas carrying wild-type IDH1. Nature medicine 403 23793099
2017 BCAT1 restricts αKG levels in AML stem cells leading to IDHmut-like DNA hypermethylation. Nature 304 29144447
2017 Branched-chain amino acid transaminase 1 (BCAT1) promotes the growth of breast cancer cells through improving mTOR-mediated mitochondrial biogenesis and function. Biochemical and biophysical research communications 173 28235484
2020 Tumour-reprogrammed stromal BCAT1 fuels branched-chain ketoacid dependency in stromal-rich PDAC tumours. Nature metabolism 165 32694827
2013 Over-expression of BCAT1, a c-Myc target gene, induces cell proliferation, migration and invasion in nasopharyngeal carcinoma. Molecular cancer 127 23758864
2015 Evaluation of an assay for methylated BCAT1 and IKZF1 in plasma for detection of colorectal neoplasia. BMC cancer 101 26445409
2015 BCAT1 expression associates with ovarian cancer progression: possible implications in altered disease metabolism. Oncotarget 90 26372729
2016 A Blood Test for Methylated BCAT1 and IKZF1 vs. a Fecal Immunochemical Test for Detection of Colorectal Neoplasia. Clinical and translational gastroenterology 87 26765125
2016 A cross-sectional study comparing a blood test for methylated BCAT1 and IKZF1 tumor-derived DNA with CEA for detection of recurrent colorectal cancer. Cancer medicine 82 27726312
2021 BCAT1 decreases the sensitivity of cancer cells to cisplatin by regulating mTOR-mediated autophagy via branched-chain amino acid metabolism. Cell death & disease 79 33568627
2014 Cytosolic branched chain aminotransferase (BCATc) regulates mTORC1 signaling and glycolytic metabolism in CD4+ T cells. The Journal of biological chemistry 79 24847056
2004 Branched-chain amino acids and neurotransmitter metabolism: expression of cytosolic branched-chain aminotransferase (BCATc) in the cerebellum and hippocampus. The Journal of comparative neurology 72 15329886
2023 Enhanced BCAT1 activity and BCAA metabolism promotes RhoC activity in cancer progression. Nature metabolism 68 37337119
2021 BCAT1 Activates PI3K/AKT/mTOR Pathway and Contributes to the Angiogenesis and Tumorigenicity of Gastric Cancer. Frontiers in cell and developmental biology 53 34164393
2018 LncRNA CRNDE promotes hepatocellular carcinoma cell proliferation, invasion, and migration through regulating miR-203/ BCAT1 axis. Journal of cellular physiology 47 30230527
2016 DOT1L histone methyltransferase regulates the expression of BCAT1 and is involved in sphere formation and cell migration of breast cancer cell lines. Biochimie 47 26783998
1999 Involvement of branched-chain amino acid aminotransferase (Bcat1/Eca39) in apoptosis. FEBS letters 46 10471790
2022 Targeting BCAT1 Combined with α-Ketoglutarate Triggers Metabolic Synthetic Lethality in Glioblastoma. Cancer research 45 35499760
2019 The role of DNMT1/hsa-miR-124-3p/BCAT1 pathway in regulating growth and invasion of esophageal squamous cell carcinoma. BMC cancer 42 31226958
2022 BCAT1 promotes osteoclast maturation by regulating branched-chain amino acid metabolism. Experimental & molecular medicine 38 35760874
2016 BCAT1 promotes tumor cell migration and invasion in hepatocellular carcinoma. Oncology letters 38 27698837
2021 Proteomic analysis of lung cancer cells reveals a critical role of BCAT1 in cancer cell metastasis. Theranostics 35 34646394
2002 Structure, function and regulation of the cyanobacterial high-affinity bicarbonate transporter, BCT1. Functional plant biology : FPB 35 32689462
2017 MicroRNA-218 inhibits tumor growth and increases chemosensitivity to CDDP treatment by targeting BCAT1 in prostate cancer. Molecular carcinogenesis 34 28052414
2022 Ruscogenin Alleviates Myocardial Ischemia-Induced Ferroptosis through the Activation of BCAT1/BCAT2. Antioxidants (Basel, Switzerland) 31 35326233
2022 BCAT1 redox function maintains mitotic fidelity. Cell reports 30 36260995
2018 BCAT1 promotes proliferation of endometrial cancer cells through reprogrammed BCAA metabolism. International journal of clinical and experimental pathology 30 31949641
2020 BCAT1 Overexpression Promotes Proliferation, Invasion, and Wnt Signaling in Non-Small Cell Lung Cancers. OncoTargets and therapy 29 32425554
2020 Evaluation of Circulating Tumor DNA for Methylated BCAT1 and IKZF1 to Detect Recurrence of Stage II/Stage III Colorectal Cancer (CRC). Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 29 32958500
2022 Assessment of tumor burden and response to therapy in patients with colorectal cancer using a quantitative ctDNA test for methylated BCAT1/IKZF1. Molecular oncology 28 35000264
2021 Oxoeicosanoid receptor inhibition alleviates acute myocardial infarction through activation of BCAT1. Basic research in cardiology 28 33484341
2021 Evaluation of a panel of tumor-specific differentially-methylated DNA regions in IRF4, IKZF1 and BCAT1 for blood-based detection of colorectal cancer. Clinical epigenetics 27 33478584
2022 BCAT1: A risk factor in multiple cancers based on a pan-cancer analysis. Cancer medicine 25 34984849
2024 Inhibition of BCAT1-mediated cytosolic leucine metabolism regulates Th17 responses via the mTORC1-HIF1α pathway. Experimental & molecular medicine 24 39085353
2020 BCAT1 binds the RNA-binding protein ZNF423 to activate autophagy via the IRE1-XBP-1-RIDD axis in hypoxic PASMCs. Cell death & disease 22 32938905
2007 Functional evidence for a nasopharyngeal carcinoma-related gene BCAT1 located at 12p12. Oncology research 22 18074675
2021 BCAT1 overexpression regulates proliferation and c‑Myc/GLUT1 signaling in head and neck squamous cell carcinoma. Oncology reports 20 33760210
2018 Branched chain amino acid transaminase 1 (BCAT1) is overexpressed and hypomethylated in patients with non-alcoholic fatty liver disease who experience adverse clinical events: A pilot study. PloS one 20 30265706
2024 BCAT1 alleviates early brain injury by inhibiting ferroptosis through PI3K/AKT/mTOR/GPX4 pathway after subarachnoid hemorrhage. Free radical biology & medicine 19 38871197
2022 The BCAT1 CXXC Motif Provides Protection against ROS in Acute Myeloid Leukaemia Cells. Antioxidants (Basel, Switzerland) 19 35453368
2020 Silencing of Long Noncoding RNA LINC00324 Interacts with MicroRNA-3200-5p to Attenuate the Tumorigenesis of Gastric Cancer via Regulating BCAT1. Gastroenterology research and practice 19 32855634
2021 Flotillin-2 promotes cell proliferation via activating the c-Myc/BCAT1 axis by suppressing miR-33b-5p in nasopharyngeal carcinoma. Aging 18 33744853
2021 BCAT1 knockdown-mediated suppression of melanoma cell proliferation and migration is associated with reduced oxidative phosphorylation. American journal of cancer research 18 34249421
2020 BCATc modulates crosstalk between the PI3K/Akt and the Ras/ERK pathway regulating proliferation in triple negative breast cancer. Oncotarget 18 32523652
2022 BCATc inhibitor 2 ameliorated mitochondrial dysfunction and apoptosis in oleic acid-induced non-alcoholic fatty liver disease model. Frontiers in pharmacology 17 36386234
2020 USF1-mediated upregulation of lncRNA GAS6-AS2 facilitates osteosarcoma progression through miR-934/BCAT1 axis. Aging 17 32269179
2020 LINC00963 Confers Oncogenic Properties in Glioma by Regulating the miR-506/BCAT1 Axis. Cancer management and research 17 32273770
2021 Long non-coding RNA TMPO-AS1 facilitates the progression of colorectal cancer cells via sponging miR-98-5p to upregulate BCAT1 expression. Journal of gastroenterology and hepatology 16 34370878
2018 Gabapentin Can Suppress Cell Proliferation Independent of the Cytosolic Branched-Chain Amino Acid Transferase 1 (BCAT1). Biochemistry 16 30427175
2023 The emerging role of the branched chain aminotransferases, BCATc and BCATm, for anti-tumor T-cell immunity. Immunometabolism (Cobham, Surrey) 15 36644500
2022 Impaired expression of BCAT1 relates to muscle atrophy of mouse model of sarcopenia. BMC musculoskeletal disorders 15 35562710
2021 Curcumin induces apoptosis by inhibiting BCAT1 expression and mTOR signaling in cytarabine‑resistant myeloid leukemia cells. Molecular medicine reports 15 34109436
2019 Data mining of the expression and regulatory role of BCAT1 in hepatocellular carcinoma. Oncology letters 15 31788061
2017 Reciprocal control of lncRNA-BCAT1 and β-catenin pathway reveals lncRNA-BCAT1 long non-coding RNA acts as a tumor suppressor in colorectal cancer. Oncotarget 15 28416735
2024 Cross-talk between BCKDK-mediated phosphorylation and STUB1-dependent ubiquitination degradation of BCAT1 promotes GBM progression. Cancer letters 14 38621458
2022 Detection of recurrent colorectal cancer with high specificity using a reporting threshold for circulating tumor DNA methylated in BCAT1 and IKZF1. Cancer 14 35290664
2021 Mutant IDH1 inhibitors activate pSTAT3-Y705 leading to an increase in BCAT1 and YKL-40 levels in mutant IDH1-expressing cells. Biochimica et biophysica acta. Molecular cell research 14 34329662
2004 Intraocular delivery of BDNF following visual cortex lesion upregulates cytosolic branched chain aminotransferase (BCATc) in the rat dorsal lateral geniculate nucleus. The European journal of neuroscience 14 15233768
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
2022 Identification of natural compounds tubercidin and lycorine HCl against small-cell lung cancer and BCAT1 as a therapeutic target. Journal of cellular and molecular medicine 13 35318805
2022 Circular RNA VPS18 Promotes Glioblastoma Progression by Regulating miR-1229-3p/BCAT1 Axis. Neurotoxicity research 13 35776379
2016 Assessment of bevacizumab resistance increased by expression of BCAT1 in IDH1 wild-type glioblastoma: application of DSC perfusion MR imaging. Oncotarget 13 27626306
2022 Detection of hypermethylated BCAT1 and IKZF1 DNA in blood and tissues of colorectal, breast and prostate cancer patients. Cancer biomarkers : section A of Disease markers 12 35253733
2022 BCAT1 promotes lung adenocarcinoma progression through enhanced mitochondrial function and NF-κB pathway activation. Journal of Zhejiang University. Science. B 12 36111572
2022 P2X1 enhances leukemogenesis through PBX3-BCAT1 pathways. Leukemia 12 36418376
2017 Validation of a Circulating Tumor-Derived DNA Blood Test for Detection of Methylated BCAT1 and IKZF1 DNA. The journal of applied laboratory medicine 12 32630973
2003 Lrmp and Bcat1 are candidates for the type I diabetes susceptibility locus Idd6. Autoimmunity 12 14563018
2024 Transcription factor EB reprograms branched-chain amino acid metabolism and promotes pancreatic cancer progression via transcriptional regulation of BCAT1. Cell proliferation 11 38938061
2019 Loss of BCAT1 Expression is a Sensitive Marker for IDH-Mutant Diffuse Glioma. Neurosurgery 11 30113684
2023 LncRNA THUMPD3-AS1 promotes invasion and EMT in gastric cancer by regulating the miR-1297/BCAT1 pathway. iScience 10 37705956
2022 Translation of a tissue epigenetic signature to circulating free DNA suggests BCAT1 as a potential noninvasive diagnostic biomarker for lung cancer. Clinical epigenetics 10 36123616
2018 BCAT1 and miR-2504: novel methylome signature distinguishes spindle/desmoplastic melanoma from superficial malignant peripheral nerve sheath tumor. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 10 30310175
2006 Expression of cytosolic branched chain aminotransferase (BCATc) mRNA in the developing mouse brain. Gene expression patterns : GEP 10 17150414
2024 BCAT1, IKZF1 and SEPT9: methylated DNA biomarkers for detection of pan-gastrointestinal adenocarcinomas. Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals 9 38644767
2024 Engineering the cyanobacterial ATP-driven BCT1 bicarbonate transporter for functional targeting to C3 plant chloroplasts. Journal of experimental botany 9 38776254
2006 Cytosolic branched chain aminotransferase (BCATc) mRNA is up-regulated in restricted brain areas of BDNF transgenic mice. Brain research 9 16828066
2025 BCAT1 is a NOTCH1 target and sustains the oncogenic function of NOTCH1. Haematologica 8 39234857
2018 [The Expression and Significance of c-myc and bcat1 in Cervical Cancer]. Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 8 30378334
2022 The proatherosclerotic function of BCAT1 in atherosclerosis development of aged-apolipoprotein E-deficient mice. Biochemical and biophysical research communications 7 36182869
2025 SIRT5-mediated BCAT1 desuccinylation and stabilization leads to ferroptosis insensitivity and promotes cell proliferation in glioma. Cell death & disease 6 40195331
2024 High expression of BCAT1 sensitizes AML cells to PARP inhibitor by suppressing DNA damage response. Journal of molecular medicine (Berlin, Germany) 6 38340163
2024 Aberrant BCAT1 expression augments MTOR activity and accelerates disease progression in chronic lymphocytic leukemia. Leukemia 6 39455853
2023 LncRNA PSMB8-AS1 increases glioma malignancy via the miR-382-3p/BCAT1 axis. Translational oncology 6 38235619
2021 Variables Associated with Detection of Methylated BCAT1 or IKZF1 in Blood from Patients Without Colonoscopically Evident Colorectal Cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 6 33500319
2024 HuR promotes castration-resistant prostate cancer progression by altering ERK5 activation via posttranscriptional regulation of BCAT1. Journal of translational medicine 5 38369471
2024 CHIP-mediated ubiquitin degradation of BCAT1 regulates glioma cell proliferation and temozolomide sensitivity. Cell death & disease 5 39075053
2024 Inhibition of BCAT1 expression improves recurrent miscarriage by regulating cellular dysfunction and inflammation of trophoblasts. Cell and tissue research 5 39356334
2024 BCAT1 contributes to the development of TKI-resistant CML. Cellular oncology (Dordrecht, Netherlands) 5 39412615
2023 BCAT1 controls embryonic neural stem cells proliferation and differentiation in the upper layer neurons. Molecular brain 5 37344908
2024 BCAT1 promotes cell proliferation, migration, and invasion via the PI3K-Akt signaling pathway in oral squamous cell carcinoma. Oral diseases 4 39056279
2024 Identify BCAT1 plays an oncogenic role and promotes EMT in KIRC via single cell RNA-seq and experiment. Frontiers in oncology 4 39324007
2022 Driving with Both Feet: Supplementing AKG While Inhibiting BCAT1 Leads to Synthetic Lethality in GBM. Cancer research 4 35788291
2019 BCAT1 and BCAT2 disruption in CHO cells has cell line-dependent effects. Journal of biotechnology 4 31465797
2018 Author Correction: BCAT1 restricts αKG levels in AML stem cells leading to IDHmut-like DNA hypermethylation. Nature 4 30069041
2025 Design, Synthesis and Biological Activity Study of γ-Aminobutyric Acid (GABA) Derivatives Containing Bridged Bicyclic Skeletons as BCAT1 Inhibitors. Molecules (Basel, Switzerland) 3 40005214
2025 BCAT1 Activation Reprograms Branched-Chain Amino Acid Metabolism and Epigenetically Promotes Inflammation in Diabetic Retinopathy. Investigative ophthalmology & visual science 3 40530920
2023 MiR-320a Acts as a Tumor Suppressor in Somatotroph Pituitary Neuroendocrine Tumors by Targeting BCAT1. Neuroendocrinology 3 37591221
2023 Knockdown of PRMT1 suppresses the malignant biological behavior of osteosarcoma cells and increases cisplatin sensitivity via c-Myc-mediated BCAT1 downregulation. Journal of biochemical and molecular toxicology 3 37700640
2025 NR4A1 deficiency promotes carotid plaque vulnerability by activating integrated stress response via targeting Bcat1. Cellular and molecular life sciences : CMLS 2 39985585
2024 A blood test measuring DNA methylation of BCAT1 and IKZF1 for detection of lung adenocarcinoma. Cancer treatment and research communications 2 39154541