Affinage

MCTS1

Malignant T-cell-amplified sequence 1 · UniProt Q9ULC4

Length
181 aa
Mass
20.6 kDa
Annotated
2026-06-10
68 papers in source corpus 28 papers cited in narrative 29 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

MCTS1 (MCT-1) is a PUA-domain-containing translational regulator and oncoprotein that, together with its obligate heterodimeric partner DENR, controls the recycling of the small (40S) ribosomal subunit at stop codons and the re-initiation of translation on transcripts bearing short upstream ORFs (PMID:16982740, PMID:25043021, PMID:30146315). Structural work places the DENR-MCT-1 heterodimer on the 40S subunit with DENR's C-terminal domain occupying a position resembling eIF1, and shows that heterodimer integrity depends on a tetrahedral zinc site formed by four conserved DENR cysteines while the MCTS1 surface (residue Phe104) mediates tRNA binding required for re-initiation (PMID:28723557, PMID:30584092, PMID:29889857). Loss-of-function studies across Drosophila, yeast and human cells establish that this complex selectively governs translation of stuORF-containing mRNAs enriched for regulatory proteins and is responsible for the bulk of 40S recycling events, with unrecycled ribosomes queuing behind stop codons in its absence (PMID:25043021, PMID:30146315, PMID:34016977). In its oncogenic capacity, MCT-1 is phosphorylated and stabilized by ERK1/2 and shortens G1 phase by elevating cyclin D1 and CDK4/6 activity (PMID:10440924, PMID:17016429), remodels translational profiles of growth-regulatory mRNAs through its PUA domain (PMID:16982740, PMID:18824261), and drives genomic instability via deregulation of DNA-damage and mitotic checkpoints (PMID:15897892, PMID:22336915). MCT-1 antagonizes p53 by promoting its ubiquitin-proteasome-mediated degradation within a mutual negative-feedback loop and amplifies Shc-Ras-MEK-ERK and PI3K/AKT survival signaling, while also reshaping the tumor microenvironment through IL-6/IL-6R signaling (PMID:17416211, PMID:21138557, PMID:23211466, PMID:24858043, PMID:30885232). In humans, complete MCTS1 deficiency selectively impairs re-initiation of JAK2, reducing IL-23 responsiveness and IFN-γ production by innate-like T cells and causing Mendelian susceptibility to mycobacterial disease (PMID:37875108).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1998 Medium

    Established MCTS1 as a candidate oncogene by showing its overexpression shortens G1 and confers anchorage-independent growth, framing it as a cell-cycle-linked transforming protein.

    Evidence Genomic amplification mapping plus overexpression and soft-agar assays in NIH3T3 fibroblasts

    PMID:9766643

    Open questions at the time
    • Molecular activity undefined
    • No endogenous loss-of-function
    • Cyclin H homology inferred, not functionally tested
  2. 1999 Medium

    Connected MCT-1 to a specific G1 checkpoint mechanism by showing it elevates cyclin D1 and CDK4/6 activity, moving beyond a phenotypic to a molecular link.

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

    PMID:10440924

    Open questions at the time
    • Mechanism by which MCT-1 raises cyclin D1 not determined
    • Overexpression-only
  3. 2001 Medium

    Showed MCT-1 is post-translationally stabilized after DNA damage and is constitutively cytoplasmic, indicating regulation at the protein rather than transcript level.

    Evidence Western blotting with protein-synthesis inhibitors and subcellular fractionation in lymphoid tumor cells

    PMID:11709712

    Open questions at the time
    • Stabilizing modification/enzyme not identified
    • Functional consequence of damage stabilization unclear
  4. 2003 Medium

    Defined the transcriptional control of MCTS1 itself, identifying a TATA-less promoter with Sp1 sites and a lymphoid-specific enhancer.

    Evidence Luciferase reporters, EMSA and Southwestern blot of the MCT-1 promoter

    PMID:12938157

    Open questions at the time
    • LMBF factor not molecularly identified
    • Promoter regulation in non-lymphoid contexts untested
  5. 2005 High

    Demonstrated reciprocally (gain and loss of function) that MCT-1 deregulates the G1/S DNA-damage checkpoint and drives genomic instability and epithelial transformation.

    Evidence siRNA and overexpression with gamma-H2AX/53BP1 foci, flow cytometry and Western blotting in human epithelial cells

    PMID:15897892

    Open questions at the time
    • Direct molecular target linking MCT-1 to checkpoint proteins not established
  6. 2006 High

    Identified the molecular activity of MCTS1: its PUA domain engages the mRNA cap complex and recruits the SUI1-domain protein DENR, linking MCT-1 to selective translational regulation of growth mRNAs.

    Evidence Cap-complex co-IP with PUA-domain mutants and polysome profiling with microarray

    PMID:16982740

    Open questions at the time
    • Mechanism of mRNA selectivity unresolved at this stage
    • Cap-binding mode not structurally defined
  7. 2006 High

    Placed MCT-1 downstream of MEK/ERK by showing ERK1/2 phosphorylation stabilizes the protein and is required for its proliferative function, defining an upstream regulatory kinase.

    Evidence Genetic (dominant-negative MEK) and pharmacological ERK inhibition with phospho/stability Westerns and proliferation assays

    PMID:17016429

    Open questions at the time
    • Direct phosphorylation sites not mapped
    • Whether ERK phosphorylates MCT-1 directly vs indirectly not resolved
  8. 2007 High

    Established that MCT-1 suppresses p53 by promoting its ubiquitin-proteasome degradation and relaxes S/G2-M checkpoints, defining a mechanism for genome-destabilizing oncogenesis.

    Evidence Overexpression/knockdown, proteasome inhibition, comet assay, karyotyping and immunofluorescence

    PMID:17416211

    Open questions at the time
    • Whether MCT-1 acts directly on the p53 degradation machinery not shown
  9. 2009 High

    Consolidated the ERK-MCT-1 axis as a survival pathway in lymphoma, showing knockdown induces apoptosis in vitro and reduces tumor growth in vivo.

    Evidence shRNA knockdown, ERK inhibition, apoptosis assays and DLBCL xenografts

    PMID:19789340

    Open questions at the time
    • Translational targets mediating survival not identified here
  10. 2009 Medium

    Showed genetic epistasis with p53: MCT-1 and p53 loss synergize to drive chromosomal instability and Ras-MEK-ERK amplification, defining a cooperative tumorigenic context.

    Evidence Overexpression in p53-null vs proficient cells, chromosome analysis, migration and xenograft assays

    PMID:19372582

    Open questions at the time
    • Single-lab phenotype set
    • Direct mechanism of synergy not dissected
  11. 2010 Medium

    Defined a mutual negative-feedback loop in which p53 transcriptionally represses MCTS1 while MCT-1 suppresses p53 promoter function and stimulates p53 inhibitors (MDM2, Pirh2, Cop1).

    Evidence Promoter luciferase reporters, mRNA stability assays and response-element analysis

    PMID:21138557

    Open questions at the time
    • Direct p53 binding to MCTS1 promoter shown functionally but not by definitive ChIP
    • Loop dynamics in vivo untested
  12. 2014 High

    Established the core biological function: DENR-MCT-1 are the first selective regulators of translation re-initiation, required for stuORF-containing mRNAs encoding regulatory proteins and tissue growth.

    Evidence Genetic knockdown in Drosophila with polysome profiling, uORF reporters and rescue

    PMID:25043021

    Open questions at the time
    • Structural basis of 40S engagement not yet shown
    • Mammalian target set not enumerated here
  13. 2014 Medium

    Linked MCT-1 to PI3K/AKT by showing it antagonizes PTEN and physically associates with Src and p190B, integrating translational and cytoskeletal/survival signaling.

    Evidence Co-IP (MCT-1 with Src/p190B), shRNA, PTEN and RhoA activity assays and xenografts

    PMID:24858043

    Open questions at the time
    • Whether Src/p190B binding is direct not established
    • Single-lab
  14. 2017 High

    Provided the structural mechanism by solving the human 40S-DENR-MCT-1 complex, revealing DENR's eIF1-like positioning that rationalizes its role in initiation fidelity and re-initiation.

    Evidence X-ray crystallography of the human 40S subunit with DENR-MCT-1

    PMID:28723557

    Open questions at the time
    • mRNA and tRNA positions not resolved in this structure
  15. 2017 Medium

    Extended the re-initiation function to human cells, identifying ~100 stuORF-dependent targets enriched for neuronal genes and GPCRs.

    Evidence siRNA of DENR/MCTS1 with polysome profiling and stuORF reporters in human cells

    PMID:28623304

    Open questions at the time
    • Target list putative
    • Physiological consequences of neuronal targets not tested
  16. 2018 High

    Resolved heterodimer architecture, showing a DENR zinc site (C34/C37/C44/C53) is essential for the MCT-1-binding interface.

    Evidence 2.0-Å crystal structure with cysteine-to-alanine mutagenesis and dimerization assays

    PMID:30584092

    Open questions at the time
    • Whether zinc-site disruption phenocopies re-initiation loss in cells not shown here
  17. 2018 High

    Defined the residues governing dimerization and tRNA binding (DENR E42/Y43/Y46; MCTS1 F104), and showed the complex binds tRNA ribosome-independently like eIF2, mechanistically explaining re-initiation.

    Evidence DENR-MCTS1 crystal structure, mutagenesis, tRNA-binding and reinitiation reporter assays in human cells

    PMID:29889857

    Open questions at the time
    • tRNA species selectivity not characterized
    • In vivo tRNA delivery step not directly visualized
  18. 2018 High

    Defined the conserved in vivo activity of MCT-1/DENR orthologs as 40S recycling factors, showing knockout causes 80S queuing at stop codons and 3'UTR reinitiation.

    Evidence Ribosome profiling of yeast TMA20/TMA22 deletions, 3'UTR reporters and in vitro translation

    PMID:30146315

    Open questions at the time
    • Relative contribution vs eIF2D quantified later
    • Mammalian recycling not directly measured here
  19. 2021 High

    Quantified recycling activity using 40S-specific footprinting, showing the MCT-1/DENR heterodimer mediates the majority of 40S recycling and that a disease mutation in DENR abolishes it.

    Evidence 40S ribosome footprinting in yeast deletion strains plus autism-mutation analysis

    PMID:34016977

    Open questions at the time
    • Mechanism distinguishing recycling from reinitiation outcomes not fully resolved
  20. 2022 Medium

    Identified a deubiquitination-stabilization role in which MCTS1 binds LARP7, extends its half-life and reduces its ubiquitination to drive cell-cycle progression in laryngeal cancer.

    Evidence Co-IP, cycloheximide chase and ubiquitination Co-IP with cell-cycle Westerns

    PMID:35274760

    Open questions at the time
    • Whether MCTS1 binding is direct vs complex-mediated unclear
    • Mechanism linking binding to reduced ubiquitination not defined
  21. 2023 Medium

    Showed MCTS1 stabilizes the oncofetal regulator LIN28B by enhancing OTUD6B-1-mediated removal of K48 ubiquitin chains, expanding its protein-stabilizing repertoire.

    Evidence Co-IP, K48-chain ubiquitination assays, shRNA and proliferation assays in laryngeal carcinoma

    PMID:37634410

    Open questions at the time
    • Direct enzymatic role of MCTS1 in deubiquitination not established
    • Single tumor type
  22. 2023 High

    Defined the human disease phenotype: complete MCTS1 deficiency selectively impairs JAK2 re-initiation, blunting IL-23 responses and IFN-γ production by innate-like T cells, causing Mendelian susceptibility to mycobacterial disease.

    Evidence Patient genetics, JAK2 Westerns across cell types, cytokine-signaling and IFN-γ assays upon mycobacterial challenge

    PMID:37875108

    Open questions at the time
    • Why JAK2 is uniquely sensitive among targets not fully explained
    • Therapeutic correction untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MCT-1's translational re-initiation/recycling function mechanistically connects to its protein-stabilization (deubiquitination) and oncogenic signaling activities, and how target selectivity (e.g., JAK2) is determined, remains unresolved.
  • No unified model linking ribosome recycling to p53/PTEN/LARP7/LIN28B regulation
  • Determinants of mammalian target selectivity undefined
  • Direct vs indirect roles in protein stabilization unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0045182 translation regulator activity 6 GO:0060090 molecular adaptor activity 4 GO:0003723 RNA binding 1
Localization
GO:0005840 ribosome 3 GO:0005829 cytosol 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-8953854 Metabolism of RNA 4 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-168256 Immune System 1
Partners
DENRLARP7OTUD6BP190BSRCTWF1
Complex memberships
40S ribosomal subunit (DENR-MCT-1 bound)DENR-MCTS1 heterodimer

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 MCT-1 (MCTS1) is a novel oncogene localized to chromosome Xq22-24 that, when overexpressed in NIH3T3 fibroblasts, shortens G1 phase and promotes anchorage-independent growth. Amino acid homology to a protein-protein binding domain of cyclin H was identified, suggesting a role in cell cycle regulation. AP-PCR genomic amplification assay, FISH mapping, overexpression in NIH3T3 cells with proliferation and soft agar colony assays Cancer research Medium 9766643
1999 Overexpression of MCT-1 in NIH3T3 fibroblasts increases cdk4 and cdk6 kinase activity, elevates cyclin D1 protein levels, and enhances G1 cyclin/cdk complex formation, establishing a mechanistic link between MCT-1 and G1 phase cell cycle checkpoint deregulation. Kinase activity assays, Western blotting, immunoprecipitation in MCT-1-overexpressing NIH3T3 cells Journal of cellular biochemistry Medium 10440924
2001 MCT-1 protein is stabilized in response to DNA damaging agents (gamma irradiation) without requiring new protein synthesis, indicating post-translational stabilization. MCT-1 protein is constitutively cytoplasmic throughout the cell cycle in human lymphoid tumor cells. Western blotting after irradiation with and without protein synthesis inhibitors; subcellular fractionation and immunofluorescence Oncogene Medium 11709712
2003 The MCT-1 promoter contains a TATA-less region with a consensus initiator element and two Sp1 sites for basal transcription. A positive cis-acting enhancer element at -133 to -122 was identified that binds a lymphoid-specific factor (LMBF, ~96 kDa), and this element functions as an enhancer in reverse orientation. Luciferase reporter assays, electrophoretic mobility shift assay (EMSA), Southwestern blot, deletion analysis of the MCT-1 promoter Journal of cellular biochemistry Medium 12938157
2005 MCT-1 overexpression deregulates cell cycle checkpoints: it enhances phosphorylation of H2AX and NBS1, increases DNA damage-induced gamma-H2AX and 53BP1 foci, preferentially increases S-phase population after gamma-irradiation, and causes a G1/S checkpoint defect. MCT-1 also transforms immortalized human mammary epithelial cells and promotes genomic instability. Knockdown of MCT-1 via siRNA attenuates H2AX phosphorylation and the checkpoint defect. siRNA knockdown, overexpression, flow cytometry, immunofluorescence for gamma-H2AX and 53BP1 foci, Western blotting for checkpoint proteins 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 upregulation modulates the translational profiles (polysome association) of BCL2L2, TFDP1, MRE11A, cyclin D1, and E2F1 mRNAs without changing total cytoplasmic mRNA levels. Co-immunoprecipitation with cap complex, PUA domain mutant analysis, polysome fractionation with microarray analysis of polysome-associated mRNAs Cancer research High 16982740
2006 MCT-1 protein is phosphorylated by p44/p42 MAPK (ERK1/2), and this phosphorylation is critical for MCT-1 protein stabilization and its ability to promote cell proliferation. Both genetic (dominant-negative MEK) and pharmacological (MEK/ERK inhibitors) approaches demonstrated that blocking ERK activity reduces MCT-1 phosphorylation and stability. Pharmacological and genetic inhibition of MEK/ERK, Western blotting for MCT-1 phosphorylation and protein stability, proliferation assays Oncogene High 17016429
2007 Forced induction of MCT-1 decreases p53 expression before and after genomic insults by promoting ubiquitin-dependent proteosomal degradation of p53 (increased ubiquitinated-p53 and phospho-MDM2 levels). MCT-1 also enhances ERK1/ERK2 phosphorylation, and MEK/ERK inhibition or MCT-1 knockdown elevates genotoxin-induced p53 and p21 production. MCT-1 overexpression relaxes S-phase and G2/M checkpoints and causes nuclear MCT-1 redistribution upon genotoxic stress coinciding with gamma-H2AX foci. Overexpression and knockdown of MCT-1, proteasome inhibitor treatment, Western blotting, flow cytometry, alkaline comet assay, spectral karyotyping, immunofluorescence DNA repair High 17416211
2008 A PUA-domain mutant of MCT-1 expressed in human lymphoma cell lines reduces anchorage-independent growth, increases susceptibility to apoptosis, and alters the translational profile of target mRNAs, confirming that the PUA domain is required for MCT-1's oncogenic translational regulatory function. PUA-domain mutant overexpression, soft agar colony assay, apoptosis assay, polysome fractionation and translational profile analysis Leukemia research Medium 18824261
2009 MCT-1 is phosphorylated and upregulated by extracellular signal-regulated kinase (ERK); pharmacological ERK inhibition disrupts MCT-1 phosphorylation and stability. MCT-1 knockdown by shRNA in DLBCL cells induces apoptosis. A functional molecular interaction between MCT-1 and the MEK/ERK signaling pathway is established. shRNA knockdown, ERK inhibitor treatment, Western blotting for MCT-1 phosphorylation, apoptosis assays, in vivo DLBCL xenograft model Cancer research High 19789340
2009 MCT-1 overexpression accelerates p53 degradation via the ubiquitin-proteasome pathway. In p53-deficient cells, MCT-1 further increases chromosomal translocations, deregulates G2/M checkpoint, promotes chromosome copy number gain, multinucleation, and cytokinesis failure, and amplifies Ras-MEK-ERK signaling and metastatic molecule expression. Loss of p53 and MCT-1 overexpression synergistically promote tumorigenesis. Overexpression in p53-deficient and p53-proficient cells, chromosome analysis, flow cytometry for cell cycle, migration/adhesion assays, xenograft tumorigenicity assays Molecular cancer research Medium 19372582
2010 MCT-1 is a novel target gene of p53 transcriptional regulation: wild-type p53 (but not mutant p53) suppresses MCT-1 promoter activity and MCT-1 mRNA stability. In a negative feedback loop, constitutively expressed MCT-1 decreases p53 promoter function and p53 mRNA stability. MDM2, Pirh2, and Cop1 (inhibitors of p53) are stimulated by MCT-1 oncoprotein. Promoter luciferase reporter assays, mRNA stability assays, Western blotting, p53 response element analysis, ChIP-like functional assays Molecular cancer Medium 21138557
2012 MCT-1 is a centrosomal oncoprotein involved in mitosis. Knockdown of MCT-1 causes intercellular bridging, chromosome mis-congregation, cytokinesis delay, and mitotic death. MCT-1 overexpression in p53-deficient cells deregulates mitotic checkpoint kinases and proteins, increasing cytokinesis failure, multinucleation, centrosome amplification, polyploidy, and aneuploidy. shRNA knockdown, overexpression, immunofluorescence for centrosome markers, flow cytometry for ploidy, time-lapse microscopy of mitotic progression Cell cycle Medium 22336915
2012 MCT-1 acts as a novel regulator of Shc-Ras-MEK-ERK signaling. Knockdown of MCT-1 enhances apoptotic cell death with caspase activation and suppresses cancer cell proliferation, chemo-resistance and tumorigenic capacity. Shc pathway activity measurement, MCT-1 knockdown, caspase activity assays, xenograft tumor assays Oncotarget Medium 23211466
2014 DENR and MCT-1 are the first identified selective regulators of eukaryotic translation re-initiation. mRNAs containing upstream ORFs with strong Kozak sequences (stuORFs) selectively require DENR-MCT-1 for their translation. Loss of DENR or MCT-1 in Drosophila impairs tissue growth by reducing translation of a specific class of mRNAs enriched for regulatory proteins including oncogenic kinases. Genetic knockdown of DENR and MCT-1 in Drosophila, polysome profiling, reporter assays for uORF-containing mRNA translation, rescue experiments, tissue growth phenotype analysis Nature High 25043021
2014 MCT-1 overexpression antagonizes PTEN gene presentation, protein stability, and functional activity, further promoting PI3K/AKT signaling. In PTEN-null cancer cells, MCT-1 interacts with p190B and Src in vivo. MCT-1 overexpression and PTEN loss synergistically augment Src/p190B signaling, inhibit RhoA activity, and drive neoplastic multinucleation via spindle multipolarity and cytokinesis failure. Co-immunoprecipitation (MCT-1 with p190B and Src), shRNA knockdown, PTEN activity assays, RhoA activity assay, xenograft tumorigenicity assay, immunofluorescence Oncogene Medium 24858043
2017 Crystal structure of the human small ribosomal subunit in complex with DENR-MCT-1 was determined. The structure reveals that DENR-MCT-1 binds the 40S subunit and the C-terminal domain of DENR occupies a position with striking similarity to canonical eIF1, which controls fidelity of translation initiation and scanning, providing a mechanistic basis for DENR-MCT-1 function in translation initiation and reinitiation. X-ray crystallography of human 40S ribosomal subunit in complex with DENR-MCT-1 Cell reports High 28723557
2017 In human cells, transcripts with short upstream ORFs (stuORFs) of only 1 amino acid are selectively dependent on DENR and MCTS1 for optimal translation, identifying ~100 putative DENR/MCTS1 translational targets enriched for neuronal genes and G protein-coupled receptors. siRNA knockdown of DENR and MCTS1 in human cells, polysome profiling, reporter assays with stuORF-containing mRNAs Scientific reports Medium 28623304
2017 MCT-1 activation promotes YY1-EGFR-MnSOD signaling: MCT-1 overexpression suppresses p53 accumulation, elevates MnSOD via the YY1-EGFR signaling cascade, generates intracellular ROS and mitochondrial superoxide, and protects cells against oxidative damage. MCT-1 overexpression in lung cancer cells promotes tumor progression and increases tumor-associated M2 macrophages and cancer-associated fibroblasts. Overexpression and knockdown, Western blotting, ROS measurement, EGFR inhibition, in vivo lung tumor xenograft model Oncogenesis Medium 28394354
2018 Crystal structure of the human DENR-MCT-1 heterodimer was determined at 2.0-Å resolution. Four conserved cysteine residues of DENR (C34, C37, C44, C53) form a tetrahedral zinc ion-binding site essential for preserving DENR's MCT-1-binding interface; substitution of all four cysteines with alanine abolished heterodimer formation. X-ray crystallography, site-directed mutagenesis of zinc-coordinating cysteines, biochemical heterodimer formation assay Proceedings of the National Academy of Sciences High 30584092
2018 Crystal structure of MCTS1 bound to a fragment of DENR was determined. DENR residues Glu42, Tyr43, and Tyr46 are required for MCTS1 binding; MCTS1 residue Phe104 is required for tRNA binding. DENR-MCTS1 dimerization and tRNA binding are both necessary for the complex to promote translation reinitiation in human cells. The DENR-MCTS1 complex can bind tRNA in the absence of the ribosome, suggesting it recruits tRNA analogously to eIF2 in cap-dependent translation. Crystal structure of DENR-MCTS1, site-directed mutagenesis (DENR E42A/Y43A/Y46A and MCTS1 F104A), tRNA binding assays, reinitiation reporter assays in human cells PLoS biology High 29889857
2018 Tma20 (MCT-1), Tma22 (DENR), and Tma64 (eIF2D) function as 40S ribosomal subunit recycling factors in vivo in yeast. Deletion of these genes causes 80S ribosomes to queue behind stop codons (block in 40S recycling), with unrecycled ribosomes able to reinitiate at AUG codons in the 3' UTR. The Tma20/Tma22 (MCT-1/DENR) pathway promotes 40S recycling and can lead to 80S reinitiation in 3' UTRs. Ribosome profiling (Ribo-seq) of yeast deletion strains, 3' UTR reporter assays, in vitro translation with uORF-containing mRNAs Molecular cell High 30146315
2019 MCT-1 stimulates IL-6 secretion, which promotes monocytic THP-1 polarization into M2-like macrophages and increases TNBC cell invasiveness. MCT-1 elevates soluble IL-6 receptor levels. MCT-1 knockdown induces miR-34a, which inhibits IL-6R expression and activates M1 polarization. MCT-1 increases breast cancer stem cell features further advanced by IL-6 but prevented by tocilizumab (IL-6R antibody). MCT-1 overexpression and shRNA knockdown, IL-6 ELISA, macrophage polarization assays, miR-34a measurement, tocilizumab treatment, invasion assays, xenograft mouse model Molecular cancer High 30885232
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 (BT-474 and MCF-7). Co-immunoprecipitation (direct binding), Western blotting for cyclin D1 and C-Myc protein levels upon MCTS1 modulation OncoTargets and therapy Low 32606753
2021 40S ribosome footprinting directly demonstrated that deletion of TMA20 (MCT-1) and TMA22 (DENR) genes in yeast causes broad accumulation of unrecycled 40S subunits at stop codons. The Tma20/Tma22 heterodimer is responsible for the majority of 40S recycling events while Tma64 (eIF2D) plays a minor role. An autism-associated mutation in TMA22 abolishes 40S recycling activity. 40S-specific ribosome footprinting in yeast deletion strains, TMA22 autism mutation analysis Nature communications High 34016977
2022 MCTS1 interacts with LARP7 via Co-IP (mainly in the cytoplasm), increases LARP7 protein half-life, and reduces LARP7 poly-ubiquitination, thereby enhancing LSCC cell viability and cell cycle progression (CDK1, CDK2, cyclin A2, cyclin B1). LARP7 overexpression partly reversed the effects of MCTS1 knockdown. Co-immunoprecipitation, cycloheximide chase assay, ubiquitination Co-IP assay, knockdown/overexpression with cell cycle marker Western blotting Clinical and experimental pharmacology & physiology Medium 35274760
2023 MCTS1 interacts with OTUD6B isoform 1 (OTUD6B-1) in laryngeal squamous cell carcinoma cells, and MCTS1 negatively modulates LIN28B degradation by enhancing OTUD6B-1-mediated cleavage of K48-branched ubiquitin chains from LIN28B, thereby stabilizing LIN28B and promoting cyclin D1, cyclin E1, and c-Myc expression. Co-immunoprecipitation (MCTS1-OTUD6B-1 interaction), ubiquitination assays (K48-branched chains), shRNA knockdown, in vitro and in vivo proliferation assays Biochemical and biophysical research communications Medium 37634410
2023 Complete MCTS1 deficiency in humans impairs translation re-initiation of a subset of proteins including JAK2 in all cell types tested (T lymphocytes and phagocytes). Reduced JAK2 expression impairs cellular responses to IL-23 and partially IL-12, but not other JAK2-dependent cytokines. Defective IL-23 responses preferentially impair IFN-γ production by MAIT cells and γδ T lymphocytes upon mycobacterial challenge, causing Mendelian susceptibility to mycobacterial disease. Genetic analysis of MCTS1-deficient patients, Western blotting for JAK2 in multiple cell types, functional assays of cytokine signaling (IL-23, IL-12 responses), IFN-γ production assays upon mycobacterial stimulation Cell High 37875108
2010 MCT-1 promoter activity is suppressed by wild-type p53 (containing p53 response elements in the promoter region), while constitutive MCT-1 expression decreases p53 promoter function and p53 mRNA stability, establishing a mutual negative feedback loop at the transcriptional level. Luciferase reporter assays with MCT-1 promoter containing p53 response elements, mRNA stability assays, ChIP-type analysis Molecular cancer Medium 21138557

Source papers

Stage 0 corpus · 68 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 364 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 150 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) 90 11896024
2016 Lactate/pyruvate transporter MCT-1 is a direct Wnt target that confers sensitivity to 3-bromopyruvate in colon cancer. Cancer & metabolism 78 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
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 57 37399358
1998 A novel candidate oncogene, MCT-1, is involved in cell cycle progression. Cancer research 57 9766643
2017 Crystal Structure of the Human Ribosome in Complex with DENR-MCT-1. Cell reports 52 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
2023 Human MCTS1-dependent translation of JAK2 is essential for IFN-γ immunity to mycobacteria. Cell 34 37875108
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
2010 Effect of training and detraining on monocarboxylate transporter (MCT) 1 and MCT4 in Thoroughbred horses. Experimental physiology 30 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
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 24 38505617
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 23 24858043
2006 Glucose affects monocarboxylate cotransporter (MCT) 1 expression during mouse preimplantation development. Reproduction (Cambridge, England) 22 16514190
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 17 23187830
2019 A novel oral prodrug-targeting transporter MCT 1: 5-fluorouracil-dicarboxylate monoester conjugates. Asian journal of pharmaceutical sciences 15 32104489
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
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
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 10 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 10 38433101
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
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
2026 Complete and partial forms of X-linked MCTS1 deficiency in patients with mycobacterial disease. Journal of human immunity 1 41623352
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 Lactic acid induces dendritic cell pyroptosis through MCT-1 to promote tumor immune evasion. Oncogene 0 42177282
2025 Aberrant expression of MAPK1 and MCTS1 in chronic myeloid leukemia (CML). microPublication biology 0 41050328

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