Affinage

MCTS1

Malignant T-cell-amplified sequence 1 · UniProt Q9ULC4

Length
181 aa
Mass
20.6 kDa
Annotated
2026-04-28
67 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MCTS1 (MCT-1) is a translation factor and oncoprotein that heterodimerizes with DENR to promote 40S ribosomal subunit recycling at stop codons and selective translation re-initiation on mRNAs bearing short upstream ORFs with strong Kozak sequences, thereby controlling translation of specific transcripts including JAK2 and cell-cycle regulators (PMID:25043021, PMID:30146315, PMID:34016977, PMID:37875108). Structurally, the DENR–MCTS1 complex binds the 40S subunit at a site mimicking eIF1, with a zinc-dependent DENR interface stabilizing the heterodimer and MCTS1 residue Phe104 mediating tRNA recruitment (PMID:28723557, PMID:30584092, PMID:29889857). MCTS1 also functions as an oncogene: its PUA domain mediates association with the mRNA cap complex, and overexpression activates cyclin D1/cdk4/cdk6-driven G1 progression, promotes MDM2-dependent p53 degradation, engages Ras-MEK-ERK signaling—which reciprocally phosphorylates and stabilizes MCTS1—and suppresses thrombospondin-1 to enable angiogenesis (PMID:9766643, PMID:10440924, PMID:17016429, PMID:19372582, PMID:16322206, PMID:16982740). Complete human MCTS1 deficiency causes an X-linked inborn error of immunity characterized by impaired JAK2-dependent IL-23 signaling and reduced IFN-γ production by MAIT and γδ T cells upon mycobacterial challenge (PMID:37875108).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1998 High

    The first evidence that MCTS1 is an oncogene came from showing that its overexpression shortens G1 and transforms fibroblasts, establishing it as a cell-cycle–promoting factor.

    Evidence Overexpression in NIH3T3 cells with cell cycle analysis and soft agar assay

    PMID:9766643

    Open questions at the time
    • Molecular target and mechanism of G1 shortening unknown
    • No endogenous loss-of-function data
  2. 1999 High

    The G1-shortening mechanism was connected to specific cyclin-dependent kinases: MCTS1 overexpression elevates cyclin D1 and activates cdk4/cdk6, placing it upstream of the G1/S restriction point machinery.

    Evidence Kinase activity assays and co-immunoprecipitation in MCT-1-overexpressing NIH3T3 cells

    PMID:10440924

    Open questions at the time
    • Whether MCTS1 directly binds cyclin D1 or acts indirectly unknown
    • Mechanism of cyclin D1 upregulation (transcriptional vs translational) not resolved
  3. 2005 High

    MCTS1 was shown to deregulate DNA damage checkpoints (impairing G1/S arrest, increasing γ-H2AX foci and genomic instability) and to promote angiogenesis via TSP1 suppression, expanding its oncogenic repertoire beyond proliferation.

    Evidence siRNA knockdown and overexpression with γ-irradiation, flow cytometry, immunofluorescence; xenograft angiogenesis assays with TSP1 rescue

    PMID:15897892 PMID:16322206

    Open questions at the time
    • Direct mechanism of TSP1 downregulation unknown
    • Whether checkpoint defects are transcriptional or translational not distinguished
  4. 2006 High

    Two critical mechanistic advances: (1) MCTS1's PUA domain was found to interact with the mRNA cap complex and recruit DENR, altering polysome-level translational profiles of cancer-related mRNAs without changing their cytoplasmic levels; (2) ERK1/2-mediated phosphorylation was shown to stabilize MCTS1 protein, establishing a Ras-MEK-ERK feedforward loop.

    Evidence Co-IP with cap complex, polysome microarray, PUA mutant analysis; MEK inhibitors and dominant-negative ERK with phosphorylation and stability assays

    PMID:16982740 PMID:17016429

    Open questions at the time
    • Specific phosphorylation sites on MCTS1 not mapped
    • Whether DENR recruitment to cap complex is direct or bridged unclear
  5. 2007 High

    MCTS1 was found to suppress p53 through MDM2-dependent ubiquitin-proteasomal degradation and to engage a reciprocal transcriptional feedback loop with p53, explaining how MCTS1 overexpression disables both G1/S and G2/M checkpoints.

    Evidence Proteasome inhibition rescue, siRNA, luciferase reporters, mRNA stability assays, cytogenetics

    PMID:17416211 PMID:19372582 PMID:21138557

    Open questions at the time
    • Whether MCTS1 directly binds MDM2 or acts through ERK-mediated MDM2 phosphorylation not resolved
    • Contribution of transcriptional versus translational p53 suppression in vivo unclear
  6. 2012 Medium

    MCTS1's oncogenic activities were extended to centrosome biology and Src signaling: it localizes to centrosomes, and its combined overexpression with PTEN loss activates Src/p190B to inhibit RhoA, causing spindle multipolarity, cytokinesis failure, and multinucleation.

    Evidence Co-IP of MCTS1 with p190B/Src, shRNA, immunofluorescence of centrosomes, xenograft models

    PMID:22336915 PMID:24858043

    Open questions at the time
    • Whether centrosomal localization is direct or via an adaptor unknown
    • Mechanism linking MCTS1 to PTEN destabilization unresolved
  7. 2014 High

    A paradigm shift: DENR–MCTS1 was identified as the first selective regulator of eukaryotic translation re-initiation, showing that mRNAs with short uORFs bearing strong Kozak sequences require this heterodimer for downstream ORF translation—explaining MCTS1's translational selectivity.

    Evidence Drosophila loss-of-function genetics, ribosome profiling, in vitro translation, polysome analysis

    PMID:25043021

    Open questions at the time
    • How DENR–MCTS1 mechanistically enables scanning past uORF stop codons not determined
    • Whether all uORF-dependent targets are affected equally unclear
  8. 2017 High

    Structural determination of DENR–MCTS1 on the 40S subunit revealed that DENR's C-terminal domain occupies the eIF1-binding site, and genome-wide analysis in human cells refined the target repertoire to mRNAs with single-amino-acid stuORFs (~100 genes enriched for neuronal functions and GPCRs).

    Evidence X-ray crystallography of 40S•DENR–MCTS1 complex; siRNA knockdown with polysome profiling and reporters in human cells

    PMID:28623304 PMID:28723557

    Open questions at the time
    • Functional consequence of eIF1-mimicry for start-codon fidelity not tested
    • Neuronal phenotypes of DENR/MCTS1 loss in mammals not yet established
  9. 2018 High

    Three key advances consolidated the structural and functional mechanism: (1) a zinc-binding site in DENR (C34/C37/C44/C53) was shown to be essential for heterodimer formation; (2) MCTS1 Phe104 was identified as critical for tRNA binding, which is required for re-initiation activity; (3) yeast ribosome profiling directly demonstrated that Tma20/Tma22 (MCT-1/DENR orthologs) are the primary 40S recycling factors at stop codons.

    Evidence Crystal structures at 2.0 Å, mutagenesis of zinc-coordinating cysteines and Phe104, tRNA binding assays, 40S ribosome profiling in yeast deletion strains

    PMID:29889857 PMID:30146315 PMID:30584092

    Open questions at the time
    • Whether tRNA binding occurs before or after 40S engagement unknown
    • Structural basis for uORF-length selectivity not resolved
  10. 2021 High

    40S-specific ribosome footprinting directly confirmed that MCTS1/DENR orthologs perform the majority of 40S recycling at stop codons in vivo, and an autism-associated DENR mutation abolished recycling activity, linking the pathway to neurological disease.

    Evidence 40S-specific ribosome profiling in yeast, autism-associated mutant knock-in

    PMID:34016977

    Open questions at the time
    • Whether the autism-associated phenotype in humans is driven solely by recycling defect not established
    • Mammalian 40S footprinting not yet performed
  11. 2023 High

    Complete human MCTS1 deficiency was characterized: it specifically impairs translation re-initiation of JAK2, reducing IL-23-driven IFN-γ production by MAIT and γδ T cells and causing susceptibility to mycobacterial disease, while being otherwise physiologically redundant—providing direct human validation of the re-initiation mechanism.

    Evidence Human X-linked recessive patients, JAK2 protein quantification, cytokine response assays across multiple cell types and kindreds

    PMID:37875108

    Open questions at the time
    • Full spectrum of translationally affected targets in MCTS1-deficient humans not catalogued
    • Whether MCTS2 partially compensates in human tissues not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: (1) the structural basis for uORF-length selectivity in DENR–MCTS1-dependent re-initiation; (2) the relative contribution of translational re-initiation versus signaling (ERK, Src, p53) functions to MCTS1's oncogenic activity in vivo; (3) whether MCTS2 serves as a physiologically relevant alternative partner for DENR; and (4) the mechanism by which MCTS1 interacts with centrosomes and influences mitotic fidelity.
  • No structural model of uORF-length discrimination
  • No separation-of-function mutant distinguishing translational versus signaling roles in cancer
  • MCTS2 redundancy in mammalian tissues uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0045182 translation regulator activity 7 GO:0098772 molecular function regulator activity 5 GO:0003723 RNA binding 2
Localization
GO:0005829 cytosol 2 GO:0005840 ribosome 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-392499 Metabolism of proteins 6 R-HSA-162582 Signal Transduction 5 R-HSA-1640170 Cell Cycle 4 R-HSA-1643685 Disease 4
Complex memberships
DENR–MCTS1 heterodimer

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 MCTS1 (MCT-1) overexpression decreases cell-doubling time by shortening the G1 phase of the cell cycle without increasing S and G2-M phases, and transforms NIH3T3 fibroblasts (anchorage-independent growth). The protein shares limited amino acid homology with a protein-protein binding domain of cyclin H. Overexpression in NIH3T3 cells, cell cycle analysis, soft agar colony formation assay Cancer research High 9766643
1999 MCT-1 overexpression in NIH3T3 fibroblasts increases cdk4 and cdk6 kinase activity, elevates cyclin D1 protein levels, and increases G1 cyclin/cdk complex formation, mechanistically linking MCT-1 to deregulation of G1/S checkpoint kinases. Kinase activity assays (cdk4, cdk6), Western blotting, co-immunoprecipitation in MCT-1-overexpressing NIH3T3 cells Journal of cellular biochemistry High 10440924
2001 MCT-1 protein is stabilized in response to DNA damaging agents (gamma irradiation) without new protein synthesis, indicating post-translational stabilization. MCT-1 is localized to the cytoplasm throughout the cell cycle in human lymphoid tumor cells. Western blotting, subcellular fractionation, cell cycle synchronization, protein synthesis inhibition Oncogene Medium 11709712
2005 MCT-1 overexpression promotes angiogenesis by dramatically reducing thrombospondin-1 (TSP1) levels in breast cancer xenografts, and inhibits apoptosis. Blocking TSP1 in conditioned medium of MCT-1-negative cells restored angiogenic potential to that of MCT-1-overexpressing cells. Xenograft tumor model, microvascular density measurement, conditioned medium rescue experiment, Western blotting Cancer research Medium 16322206
2005 MCT-1 overexpression deregulates cell cycle checkpoints: it increases phosphorylation of H2AX and NBS1, increases DNA damage foci, preferentially increases S-phase population after gamma-irradiation, impairs the G1/S checkpoint, and promotes genomic instability. MCT-1 siRNA knockdown attenuates H2AX phosphorylation and the G1/S checkpoint defect. siRNA knockdown, gamma-irradiation, flow cytometry, immunofluorescence (gamma-H2AX, 53BP1 foci), transformation assay Oncogene High 15897892
2006 MCT-1 protein interacts with the mRNA cap complex through its PUA domain and recruits DENR (DRP), a protein containing the SUI1 translation initiation domain. MCT-1 overexpression modulates the translational profiles of BCL2L2, TFDP1, MRE11A, cyclin D1, and E2F1 mRNAs at the polysome level without altering cytoplasmic mRNA levels. Co-immunoprecipitation (cap complex), polysome microarray analysis, PUA domain mutant analysis Cancer research High 16982740
2006 Phosphorylation of MCT-1 by p44/p42 MAPK (ERK1/ERK2) is required for MCT-1 protein stabilization and its ability to promote cell proliferation. Genetic and pharmacological inhibition of MEK/ERK reduced MCT-1 phosphorylation and stability. Pharmacological MEK inhibitors, dominant-negative ERK, Western blotting for phosphorylated MCT-1, proliferation assays Oncogene High 17016429
2007 MCT-1 overexpression decreases p53 expression via ubiquitin-dependent proteasomal degradation (increased ubiquitinated-p53 and phospho-MDM2 levels), and activates MAPK (ERK1/ERK2) phosphorylation. MCT-1 knockdown or MEK/ERK inhibition elevates genotoxin-induced p53 and p21 production. MCT-1 nuclear allocation after genotoxic stress coincides with gamma-H2AX appearance. Western blotting, proteasome inhibition rescue, siRNA knockdown, comet assay, spectral karyotyping, immunofluorescence DNA repair High 17416211
2008 A PUA-domain mutant of MCT-1 attenuates its oncogenic function: cells expressing the PUA mutant show reduced anchorage-independent growth, increased apoptosis susceptibility, and an altered translational profile, establishing that the PUA domain is essential for MCT-1's translational regulatory activity. PUA domain mutagenesis, soft agar assay, apoptosis assay, polysome profiling Leukemia research Medium 18824261
2009 ERK phosphorylates MCT-1 and up-regulates it in DLBCL. Pharmacological ERK inhibition disrupts MCT-1 phosphorylation and stability. MCT-1 knockdown by shRNA induces apoptosis in DLBCL cells, demonstrating dependence on MCT-1 for survival. shRNA knockdown, ERK small-molecule inhibitor, phosphorylation analysis, xenograft model Cancer research High 19789340
2009 MCT-1 accelerates p53 protein degradation via ubiquitin-dependent proteolysis. MCT-1 induction in p53-deficient cells increases chromosomal translocations, deregulates G2-M checkpoint, promotes multinucleation, and activates Ras-MEK-ERK signaling. Loss of p53 and MCT-1 overexpression synergistically promote chromosome instability and tumorigenicity. Western blotting, proteasome inhibition, cell cycle analysis, cytogenetics, xenograft model, siRNA Molecular cancer research : MCR High 19372582
2010 MCT-1 promoter activity is negatively regulated by wild-type p53 (but not mutant p53) through response elements in the promoter. In a negative feedback loop, MCT-1 suppresses p53 promoter function and p53 mRNA stability. MCT-1 also constitutively stimulates p53 inhibitors MDM2, Pirh2, and COP1. Luciferase reporter assays, promoter deletion analysis, mRNA stability assays, Western blotting Molecular cancer Medium 21138557
2012 MCT-1 overexpression and PTEN loss synergistically activate Src/p190B signaling, leading to inhibition of RhoA activity, spindle multipolarity, cytokinesis failure, and neoplastic multinucleation. MCT-1 co-immunoprecipitates with p190B and Src in vivo, indicating proximity within a signaling complex. MCT-1 antagonizes PTEN protein stability and functional activity. Co-immunoprecipitation, shRNA knockdown, xenograft model, FACS, immunofluorescence Oncogene High 24858043
2012 MCT-1 is identified as a centrosomal oncoprotein. Knockdown of MCT-1 causes intercellular bridging, chromosome mis-congregation, cytokinesis delay, and mitotic death. MCT-1 combined with p53 deficiency deregulates mitotic checkpoint kinases, leading to cytokinesis failure, multi-nucleation, centrosome amplification, polyploidy, and aneuploidy. siRNA knockdown, immunofluorescence (centrosome staining), cell cycle analysis, long-term cultivation, spindle damage Cell cycle Medium 22336915
2012 MCT-1 overexpression activates Shc-Ras-MEK-ERK signaling. MCT-1 knockdown enhances apoptotic cell death with caspase activation. shRNA knockdown, Western blotting for Shc/ERK pathway components, apoptosis assay, xenograft model Oncotarget Medium 23211466
2014 DENR and MCT-1 (MCTS1) are the first selective regulators of eukaryotic translation re-initiation. mRNAs containing upstream ORFs with strong Kozak sequences selectively require DENR-MCT-1 for their translation. In Drosophila, loss of DENR or MCT-1 reduces tissue growth. Drosophila genetics (loss-of-function), reporter assays, ribosome profiling, in vitro translation, polysome analysis Nature High 25043021
2017 Crystal structure of the human small ribosomal subunit in complex with DENR-MCT-1 was determined. The C-terminal domain of DENR binds to the 40S subunit at a site strikingly similar to that of canonical eIF1, suggesting that DENR-MCT-1 controls fidelity of translation initiation and re-initiation by mimicking eIF1 function. X-ray crystallography of human 40S•DENR-MCT-1 complex Cell reports High 28723557
2017 DENR and MCTS1 regulate translation re-initiation on transcripts with short upstream ORFs (stuORFs) in human cells. Only transcripts with very short stuORFs (1 amino acid) are dependent on DENR and MCTS1, identifying ~100 human genes as DENR/MCTS1 translational targets enriched for neuronal genes and GPCRs. siRNA knockdown of DENR and MCTS1, polysome profiling, reporter assays in human cells Scientific reports High 28623304
2017 MCT-1 overexpression promotes ROS generation, suppresses p53 accumulation, and elevates MnSOD via the YY1-EGFR signaling cascade to protect cells from oxidative damage. Targeting YY1 in lung cancer cells inhibits the EGFR-MnSOD pathway and cell invasiveness induced by MCT-1. Western blotting, ROS measurement, siRNA targeting YY1, invasion assay, xenograft model Oncogenesis Medium 28394354
2018 Crystal structure of the DENR-MCT-1 heterodimer at 2.0-Å resolution reveals that four conserved DENR cysteines (C34, C37, C44, C53) form a zinc-binding site essential for heterodimer formation; substitution of all four cysteines abolished heterodimer formation. X-ray crystallography, site-directed mutagenesis of zinc-coordinating cysteines, co-immunoprecipitation Proceedings of the National Academy of Sciences High 30584092
2018 Crystal structure of MCTS1 bound to DENR fragment identifies DENR residues Glu42, Tyr43, Tyr46 as important for MCTS1 binding, and MCTS1 residue Phe104 as important for tRNA binding. DENR-MCTS1 dimerization and tRNA binding are both necessary for the complex to promote translation re-initiation in human cells. DENR-MCTS1 can bind tRNA in the absence of the ribosome, suggesting it recruits tRNA analogously to eIF2. X-ray crystallography, site-directed mutagenesis (DENR E42A/Y43A/Y46A; MCTS1 F104A), translation reporter assays in human cells, tRNA binding assay PLoS biology High 29889857
2018 Yeast Tma20 (MCT-1) and Tma22 (DENR) function as 40S ribosomal subunit recycling factors in vivo. Ribosome profiling of tma deletion strains revealed 80S ribosomes queued behind stop codons (block in 40S recycling). Unrecycled 40S subunits can reinitiate translation at AUG codons in 3' UTRs, and in vitro translation confirmed increased reinitiation in the absence of these proteins. Ribosome profiling (deletion strains), 3' UTR reporter analysis, in vitro translation with uORF reporters Molecular cell High 30146315
2019 MCT-1 stimulates IL-6 secretion that promotes monocytic THP-1 polarization into M2-like macrophages, and elevates soluble IL-6 receptor levels. MCT-1 increases breast cancer stem cell features further advanced by IL-6, which are prevented by tocilizumab (IL-6R antibody). Tumor suppressor miR-34a is induced upon MCT-1 knockdown and inhibits IL-6R expression. MCT-1 overexpression/knockdown, cytokine ELISA, macrophage polarization assay, sphere formation, miR-34a gain/loss of function Molecular cancer Medium 30885232
2021 40S ribosome footprinting directly establishes that yeast Tma20 (MCT-1)/Tma22 (DENR) heterodimer is responsible for the majority of 40S recycling events at stop codons in vivo, while Tma64 (eIF2D) plays a minor role. An autism-associated mutation in TMA22 (DENR) abolishes 40S recycling activity, linking ribosome recycling to neurological disease. 40S-specific ribosome profiling, gene deletions, autism-associated mutant knock-in Nature communications High 34016977
2023 Complete MCTS1 deficiency in humans impairs translation re-initiation of a specific subset of proteins, including JAK2, in all cell types tested (T lymphocytes, phagocytes). Reduced JAK2 expression impairs cellular responses to IL-23 (and partially IL-12), impairing IFN-γ production by MAIT and γδ T cells upon mycobacterial challenge. MCTS1 deficiency is otherwise physiologically redundant. Human genetic (X-linked recessive patients), Western blotting/expression of JAK2, cytokine response assays (IL-23, IL-12, IFN-γ), T cell functional assays Cell High 37875108
2020 MCTS1 directly binds to TWF1 (twinfilin-1) and this interaction synergistically modulates cyclin D1 and c-Myc translation in luminal A/B breast cancer cells. Co-immunoprecipitation, overexpression, Western blotting, translation analysis in BT-474 and MCF-7 cells OncoTargets and therapy Low 32606753
2022 MCTS1 interacts with LARP7 in the cytoplasm, increases LARP7 protein half-life, and reduces LARP7 poly-ubiquitination (reducing proteasomal degradation). LARP7 overexpression partially reverses MCTS1 knockdown-induced inhibitory effects on LSCC cell viability. Co-IP, cycloheximide chase assay, ubiquitination Co-IP, rescue overexpression, subcellular fractionation Clinical and experimental pharmacology & physiology Medium 35274760
2023 MCTS1 interacts with OTUD6B isoform 1 (OTUD6B-1), and this interaction enhances OTUD6B-mediated deubiquitination (cleavage of K48-branched ubiquitin chains) of LIN28B, reducing LIN28B degradation in G1/S cells and promoting cyclin D1, cyclin E1, and c-Myc expression and LSCC cell proliferation. Co-IP, ubiquitination assay (K48-branched chains), shRNA knockdown rescue, overexpression, in vitro and in vivo proliferation assays Biochemical and biophysical research communications Medium 37634410
2024 MCTS1-DENR-dependent re-initiation is accurately recapitulated in a cell-free (HeLa lysate) in vitro re-initiation assay. MCTS2 (encoded by a retrogene copy of MCTS1) can serve as an alternative DENR partner that promotes re-initiation in vitro. eIF2D knockdown causes widespread gene expression deregulation unrelated to uORF translation, establishing a distinct function from MCTS1-DENR. Cell-free re-initiation assay (HeLa lysates), ribosome profiling (siRNA knockdown), reporter assays bioRxivpreprint Medium bio_10.1101_2024.06.05.597545
2003 The MCT-1 promoter is TATA-less with a consensus initiator element and two Sp1 sites directing basal transcription. A region from -133 to -122 contains a positive cis-acting enhancer element that binds a lymphoid-specific nuclear protein (LMBF, ~96 kDa) distinct from known heat shock factors, required for maximal transcriptional activity. Luciferase reporter assays, deletion analysis, EMSA, Southwestern blot Journal of cellular biochemistry Medium 12938157

Source papers

Stage 0 corpus · 67 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 MCT-1/miR-34a/IL-6/IL-6R signaling axis promotes EMT progression, cancer stemness and M2 macrophage polarization in triple-negative breast cancer. Molecular cancer 360 30885232
1997 Comparison of lactate transport in astroglial cells and monocarboxylate transporter 1 (MCT 1) expressing Xenopus laevis oocytes. Expression of two different monocarboxylate transporters in astroglial cells and neurons. The Journal of biological chemistry 281 9374487
2014 DENR-MCT-1 promotes translation re-initiation downstream of uORFs to control tissue growth. Nature 149 25043021
2002 Luminal leptin enhances CD147/MCT-1-mediated uptake of butyrate in the human intestinal cell line Caco2-BBE. The Journal of biological chemistry 97 12034734
2002 Changes in MCT 1, MCT 4, and LDH expression are tissue specific in rats after long-term hypobaric hypoxia. Journal of applied physiology (Bethesda, Md. : 1985) 89 11896024
2016 Lactate/pyruvate transporter MCT-1 is a direct Wnt target that confers sensitivity to 3-bromopyruvate in colon cancer. Cancer & metabolism 76 27729975
2006 Testosterone increases lactate transport, monocarboxylate transporter (MCT) 1 and MCT4 in rat skeletal muscle. The Journal of physiology 76 16959859
2018 Tma64/eIF2D, Tma20/MCT-1, and Tma22/DENR Recycle Post-termination 40S Subunits In Vivo. Molecular cell 67 30146315
1998 A novel candidate oncogene, MCT-1, is involved in cell cycle progression. Cancer research 57 9766643
2023 Inhibition of lactate transport by MCT-1 blockade improves chimeric antigen receptor T-cell therapy against B-cell malignancies. Journal for immunotherapy of cancer 51 37399358
2017 Crystal Structure of the Human Ribosome in Complex with DENR-MCT-1. Cell reports 51 28723557
2017 Identification of transcripts with short stuORFs as targets for DENR•MCTS1-dependent translation in human cells. Scientific reports 46 28623304
2006 MCT-1 protein interacts with the cap complex and modulates messenger RNA translational profiles. Cancer research 43 16982740
2005 MCT-1 oncogene contributes to increased in vivo tumorigenicity of MCF7 cells by promotion of angiogenesis and inhibition of apoptosis. Cancer research 38 16322206
2003 Expression of the candidate MCT-1 oncogene in B- and T-cell lymphoid malignancies. Blood 37 12637315
2018 DENR-MCTS1 heterodimerization and tRNA recruitment are required for translation reinitiation. PLoS biology 35 29889857
2008 Monocarboxylate transporter (MCT)-1 is up-regulated by PPARalpha. Biochimica et biophysica acta 34 18375207
2021 40S ribosome profiling reveals distinct roles for Tma20/Tma22 (MCT-1/DENR) and Tma64 (eIF2D) in 40S subunit recycling. Nature communications 32 34016977
2013 Effect of AMPK activation on monocarboxylate transporter (MCT)1 and MCT4 in denervated muscle. The journal of physiological sciences : JPS 32 24081524
2005 The MCT-1 oncogene product impairs cell cycle checkpoint control and transforms human mammary epithelial cells. Oncogene 32 15897892
2023 Human MCTS1-dependent translation of JAK2 is essential for IFN-γ immunity to mycobacteria. Cell 29 37875108
2010 Effect of training and detraining on monocarboxylate transporter (MCT) 1 and MCT4 in Thoroughbred horses. Experimental physiology 29 21148623
2017 Oncogenic MCT-1 activation promotes YY1-EGFR-MnSOD signaling and tumor progression. Oncogenesis 28 28394354
1999 Increased G1 cyclin/cdk activity in cells overexpressing the candidate oncogene, MCT-1. Journal of cellular biochemistry 26 10440924
2009 Extracellular signal-regulated kinase positively regulates the oncogenic activity of MCT-1 in diffuse large B-cell lymphoma. Cancer research 25 19789340
2012 Targeting MCT-1 oncogene inhibits Shc pathway and xenograft tumorigenicity. Oncotarget 24 23211466
2009 Loss of p53 and MCT-1 overexpression synergistically promote chromosome instability and tumorigenicity. Molecular cancer research : MCR 24 19372582
2007 MCT-1 oncogene downregulates p53 and destabilizes genome structure in the response to DNA double-strand damage. DNA repair 24 17416211
1999 A model system for the study of human retinal angiogenesis: activation of monocytes and endothelial cells and the association with the expression of the monocarboxylate transporter type 1 (MCT-1). Diabetologia 24 10440131
2014 MCT-1 expression and PTEN deficiency synergistically promote neoplastic multinucleation through the Src/p190B signaling activation. Oncogene 22 24858043
2006 Glucose affects monocarboxylate cotransporter (MCT) 1 expression during mouse preimplantation development. Reproduction (Cambridge, England) 22 16514190
2024 Immunotherapeutic IL-6R and targeting the MCT-1/IL-6/CXCL7/PD-L1 circuit prevent relapse and metastasis of triple-negative breast cancer. Theranostics 20 38505617
2018 Crystal structure of the DENR-MCT-1 complex revealed zinc-binding site essential for heterodimer formation. Proceedings of the National Academy of Sciences of the United States of America 19 30584092
2006 Phosphorylation of MCT-1 by p44/42 MAPK is required for its stabilization in response to DNA damage. Oncogene 19 17016429
2012 Expression and role of GLUT-1, MCT-1, and MCT-4 in malignant pleural mesothelioma. Virchows Archiv : an international journal of pathology 16 23187830
2010 The antagonism between MCT-1 and p53 affects the tumorigenic outcomes. Molecular cancer 15 21138557
2008 Targeted suppression of MCT-1 attenuates the malignant phenotype through a translational mechanism. Leukemia research 15 18824261
2019 A novel oral prodrug-targeting transporter MCT 1: 5-fluorouracil-dicarboxylate monoester conjugates. Asian journal of pharmaceutical sciences 14 32104489
2018 PKC inhibition of sotrastaurin has antitumor activity in diffuse large B-cell lymphoma via regulating the expression of MCT-1. Acta biochimica et biophysica Sinica 14 29534146
2011 Expression of monocarboxylate transporter (MCT) 1 and MCT4 in overloaded mice plantaris muscle. The journal of physiological sciences : JPS 14 21826525
2019 Translatome and transcriptome analysis of TMA20 (MCT-1) and TMA64 (eIF2D) knockout yeast strains. Data in brief 13 30815525
2009 The anti-leukemic effect of a novel histone deacetylase inhibitor MCT-1 and 5-aza-cytidine involves augmentation of Nur77 and inhibition of MMP-9 expression. International journal of oncology 12 19148494
2007 Post-transcriptional control of the MCT-1-associated protein DENR/DRP by RNA-binding protein AUF1. Cancer genomics & proteomics 12 17878526
2001 Expression and stabilization of the MCT-1 protein by DNA damaging agents. Oncogene 11 11709712
2020 MCTS1 Directly Binds to TWF1 and Synergistically Modulate Cyclin D1 and C-Myc Translation in Luminal A/B Breast Cancer Cells. OncoTargets and therapy 10 32606753
2015 Endurance training alters basal erythrocyte MCT-1 contents and affects the lactate distribution between plasma and red blood cells in T2DM men following maximal exercise. Canadian journal of physiology and pharmacology 10 25844530
2012 The involvement of MCT-1 oncoprotein in inducing mitotic catastrophe and nuclear abnormalities. Cell cycle (Georgetown, Tex.) 10 22336915
2024 Monocarboxylate transporter-1 (MCT-1) inhibitors screened from autodisplayed FV-antibody library. International journal of biological macromolecules 9 38484814
2021 MCTS1 promotes the development of lung adenocarcinoma by regulating E2F1 expression. Oncology letters 9 34079590
2025 Focal adhesion kinase promotes aerobic glycolysis in hepatic stellate cells via the cyclin D1/c-Myc/MCT-1 pathway to induce liver fibrosis. Scientific reports 8 39915293
2024 To initiate or not to initiate: A critical assessment of eIF2A, eIF2D, and MCT-1·DENR to deliver initiator tRNA to ribosomes. Wiley interdisciplinary reviews. RNA 8 38433101
2023 MCTS1 enhances the proliferation of laryngeal squamous cell carcinoma via promoting OTUD6B-1 mediated LIN28B deubiquitination. Biochemical and biophysical research communications 8 37634410
2018 Cytotoxic action of acetate on tumor cells of thymic origin: Role of MCT-1, pH homeostasis and altered cell survival regulation. Biochimie 8 30391286
2010 Effects of age and concentrate feeding on the expression of MCT 1 and CD147 in the gastrointestinal tract of goats and Hereford finishing beef bulls. Research in veterinary science 8 20598330
2022 MCTS1 promotes laryngeal squamous cell carcinoma cell growth via enhancing LARP7 stability. Clinical and experimental pharmacology & physiology 7 35274760
2021 MCTS1 promotes invasion and metastasis of oral cancer by modifying the EMT process. Annals of translational medicine 7 34277797
2019 Multiple Copies in T-Cell Malignancy 1 (MCT-1) Promotes the Stemness of Non-Small Cell Lung Cancer Cells via Activating Interleukin-6 (IL-6) Signaling through Suppressing MiR-34a Expression. Medical science monitor : international medical journal of experimental and clinical research 7 31891569
2021 The Role of the MCTS1 and DENR Proteins in Regulating the Mechanisms Associated with Malignant Cell Transformation. Acta naturae 6 34377560
2007 The oncogene mcts1. Translational oncogenomics 4 23645982
2006 Characterization of the MCT-1 pseudogene: identification and implication of its location in a highly amplified region of chromosome 20. Biochimica et biophysica acta 3 16815567
2021 The oncogene Mct-1 promotes progression of hepatocellular carcinoma via enhancement of Yap-mediated cell proliferation. Cell death discovery 2 33753742
2003 Identification and characterization of a novel enhancer for the human MCT-1 oncogene promoter. Journal of cellular biochemistry 2 12938157
2025 circHIPK2 promotes malignant progression of laryngeal squamous cell carcinoma through the miR-889-3p/MCTS1/IL-6 axis. Translational oncology 1 40222337
2017 [Study on the relationship between MCT-1 and p53 in laryngeal squamous cell carcinoma]. Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery 1 29774995
2010 Expression and purification of recombinant human MCT-1 oncogene in insect cells. The protein journal 1 20076993
2026 Complete and partial forms of X-linked MCTS1 deficiency in patients with mycobacterial disease. Journal of human immunity 0 41623352
2025 Aberrant expression of MAPK1 and MCTS1 in chronic myeloid leukemia (CML). microPublication biology 0 41050328