Affinage

THOC1

THO complex subunit 1 · UniProt Q96FV9

Length
657 aa
Mass
75.7 kDa
Annotated
2026-04-28
64 papers in source corpus 22 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

THOC1 (Hpr1/p84) is a core subunit of the evolutionarily conserved THO/TREX complex that co-transcriptionally couples RNA polymerase II elongation with mRNA processing and nuclear export. THOC1 associates with elongating RNA Pol II, recruits the DEAD-box helicase UAP56/Sub2, and facilitates cotranscriptional loading of the mRNA export receptor Mex67/NXF1 via a direct UBA-domain interaction that modulates polyubiquitin recognition (PMID:11060033, PMID:15870275, PMID:17475778). Loss of THOC1 causes R-loop accumulation, DNA damage, and genome instability; separation-of-function mutations demonstrate that THOC1's transcription-elongation role is mechanistically distinct from its R-loop suppression function (PMID:16908536, PMID:32669125). THOC1 protein levels are regulated by ubiquitin-mediated proteasomal degradation (Rsp5 in yeast, NEDD4-1 in mammals), and THOC1 is selectively essential in rapidly proliferating and oncogene-transformed cells, where its loss triggers apoptosis and DNA damage without comparably affecting normal quiescent cells (PMID:15713680, PMID:23460917, PMID:17638875, PMID:25296641).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2000 High

    Identification of THOC1/Hpr1 as an integral subunit of the THO complex established that transcription elongation and mitotic recombination are linked through a discrete multi-protein machine.

    Evidence Affinity purification and reciprocal co-IP of tagged THO subunits in yeast with genetic deletion phenotyping

    PMID:11060033

    Open questions at the time
    • Mammalian THO complex composition not yet defined
    • Mechanism by which THO suppresses recombination unknown
  2. 2001 Medium

    Bidirectional genetic suppression between HPR1 and SUB2 placed THOC1 and the DEAD-box helicase UAP56/Sub2 in a common pathway maintaining genome stability, linking THO function to RNA helicases.

    Evidence High-copy suppressor analysis with conditional alleles in yeast

    PMID:11463828

    Open questions at the time
    • Physical interaction between Hpr1 and Sub2 not demonstrated at this stage
    • Whether suppression reflects direct binding or indirect pathway compensation unclear
  3. 2005 High

    Demonstration that human THOC1 physically associates with elongating RNA Pol II and UAP56 extended THO/TREX function to mammals and proved that THOC1 directly bridges transcription machinery with RNA processing/export factors.

    Evidence Co-IP in human cells plus siRNA-mediated depletion with transcription elongation assays

    PMID:15870275

    Open questions at the time
    • Stoichiometry of human TREX complex not resolved
    • Whether THOC1-UAP56 interaction is direct or bridged by other subunits unclear
  4. 2005 High

    Discovery that Hpr1/THOC1 is selectively poly-ubiquitinated by Rsp5/NEDD4-family E3 ligases and degraded by the proteasome revealed a post-translational mechanism controlling THO complex availability during active transcription.

    Evidence In vitro and in vivo ubiquitylation assays in yeast with proteasome inhibitors and temperature shifts; later confirmed in mammals with NEDD4-1 reconstitution

    PMID:15713680 PMID:23460917

    Open questions at the time
    • Ubiquitylation sites on THOC1 not mapped
    • Physiological signals triggering NEDD4-1-dependent degradation in mammalian cells not identified
  5. 2006 High

    A separation-of-function hpr1 point mutant showed that THOC1's transcription/export function is genetically separable from R-loop-mediated genome instability, resolving whether these were obligately linked.

    Evidence hpr1-101 mutant analyzed by transcription elongation, mRNA export, recombination, replication fork, and AID mutation assays in yeast

    PMID:16908536 PMID:19451165

    Open questions at the time
    • Structural basis for separable functions not resolved
    • Whether this separation applies to mammalian THOC1 untested
  6. 2006 High

    Thoc1-null mouse embryos arrested at implantation established THOC1 as essential for mammalian viability and showed the requirement is cell-autonomous in rapidly dividing inner cell mass cells.

    Evidence Gene knockout in mice with blastocyst outgrowth assays and immunostaining

    PMID:16705185

    Open questions at the time
    • Which transcripts are most sensitive to THOC1 loss in early embryos unknown
    • Mechanism of lethality (transcription vs. export vs. DNA damage) not dissected
  7. 2007 High

    NMR structure of the Mex67 UBA domain bound to Hpr1 revealed the atomic basis for THOC1-mediated cotranscriptional recruitment of the mRNA export receptor and showed that Hpr1 binding allosterically permits polyubiquitin recognition.

    Evidence NMR solution structure, point mutagenesis, FRET binding assays, ChIP for Mex67 recruitment, and mRNA export assays

    PMID:17475778 PMID:19451165

    Open questions at the time
    • Full-length THOC1 structure unavailable
    • Whether the mammalian NXF1-THOC1 interaction uses the same interface not confirmed
  8. 2007 High

    Selective apoptosis of oncogene-transformed cells upon THOC1 depletion, with sparing of normal isogenic cells, established THOC1 as a context-dependent survival factor for neoplastic cells.

    Evidence siRNA depletion in isogenic normal vs. E1A/Ras-transformed cells with apoptosis, γ-H2AX, and transformation assays

    PMID:17638875

    Open questions at the time
    • Which oncogenic transcripts depend most on THOC1 not identified
    • Whether selectivity holds across diverse oncogene drivers not tested
  9. 2014 High

    Conditional Thoc1 deletion in hematopoietic and prostate cancer models demonstrated lineage-selective essentiality: THOC1 is required for rapidly proliferating myeloid progenitors and cancer progression but dispensable for quiescent normal tissues.

    Evidence Conditional knockout mice with bone marrow reconstitution and autochthonous prostate cancer model with gene expression profiling

    PMID:24830368 PMID:25296641

    Open questions at the time
    • Specific gene expression programs dependent on THOC1 in myeloid progenitors not fully characterized
    • Whether THOC1 loss causes synthetic lethality with specific oncogenic pathways untested
  10. 2016 High

    Genetic epistasis between Thoc1 and Rb1 in mouse brain showed that THOC1 is required for upregulation of E2F-dependent apoptotic genes upon Rb1 loss, placing THOC1 as a functional enabler of E2F-driven transcription.

    Evidence Compound Rb1/Thoc1-hypomorphic mouse mutants with immunostaining and gene expression analysis

    PMID:27001308

    Open questions at the time
    • Whether THOC1 directly associates with E2F target gene loci not shown
    • Generalizability to other E2F-dependent contexts unknown
  11. 2020 High

    THOC1 deficiency in zebrafish causes p53-dependent hair cell apoptosis, and the human THOC1 p.L183V variant fails to rescue, linking THOC1 mutations to sensorineural phenotypes through p53 signaling.

    Evidence CRISPR-KO and morpholino in zebrafish with behavioral testing, transcriptomics, p53 inhibitor rescue, and variant-specific mRNA complementation

    PMID:32776944

    Open questions at the time
    • Whether p.L183V disrupts THO complex assembly or a specific THOC1 function not determined
    • Human patient phenotype data limited
  12. 2020 Medium

    Direct demonstration that THOC1 knockdown in hepatocellular carcinoma cells causes R-loop accumulation and DNA damage confirmed that THOC1's R-loop suppression function is relevant in human cancer cells and contributes to cisplatin sensitivity.

    Evidence siRNA knockdown with S9.6 antibody R-loop detection, γ-H2AX, cell cycle analysis, and xenograft model

    PMID:32669125

    Open questions at the time
    • Genomic loci most prone to R-loop accumulation upon THOC1 loss not mapped
    • Whether cisplatin sensitization is specific to R-loop-prone tumors unclear
  13. 2024 Medium

    Discovery that THOC1 interacts with SIN3A and prevents telomeric R-loop accumulation in glioblastoma cells extended THOC1's genome-protective role to telomere maintenance through histone deacetylation.

    Evidence CRISPR screen, co-IP of THOC1-SIN3A, S9.6 R-loop detection, ChIP for histone marks, telomere length assay in PDX lines

    PMID:41496272

    Open questions at the time
    • Whether THOC1-SIN3A interaction is direct or mediated by other subunits untested
    • Mechanism linking histone deacetylation to telomeric R-loop resolution not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full-length structure of THOC1 (alone and in the human TREX complex), identification of the specific transcripts most sensitive to THOC1 loss across cell types, the molecular basis of THOC1's selective essentiality in transformed versus normal cells, and whether THOC1 mutations cause defined human Mendelian disease.
  • No high-resolution structure of full-length mammalian THOC1
  • Genome-wide transcript sensitivity to THOC1 loss not systematically mapped
  • Causative role of THOC1 variants in human hereditary disease not established by family studies

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-8953854 Metabolism of RNA 4 R-HSA-73894 DNA Repair 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-392499 Metabolism of proteins 2 R-HSA-5357801 Programmed Cell Death 2
Partners
MFT1NEDD4NXF1SIN3ATHOC2THP2U2AF2UAP56
Complex memberships
THO complexTREX complex

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 THOC1 (yeast Tho2/Hpr1 ortholog) is a core component of the THO complex, a nuclear oligomeric complex containing Tho2, Hpr1, Mft1, and Thp2 that physically associates and functions as a unit to connect transcription elongation with mitotic recombination in yeast. Affinity purification (His6-HA-tagged THO2), reciprocal co-immunoprecipitation with anti-Mft1 antibodies, genetic deletion phenotyping The EMBO journal High 11060033
2005 Human THOC1 (hHpr1/p84/Thoc1) associates with elongating RNA polymerase II and the RNA splicing/export factor UAP56 in intact cells, and depletion of THOC1 causes transcriptional elongation defects, indicating THOC1 physically links elongating RNA Pol II with RNA processing factors in a human TREX complex. Co-immunoprecipitation in human cells, siRNA depletion with transcriptional elongation assay and cellular phenotype readout Molecular and cellular biology High 15870275
2006 Thoc1 is essential for early mouse embryonic development; homozygous null Thoc1 embryos are arrested around implantation with inner cell mass cells rapidly losing viability upon Thoc1 protein loss, demonstrating a cell-autonomous requirement for THOC1 in mammalian cell viability. Gene knockout in mice, blastocyst outgrowth assay, immunostaining for Thoc1 protein loss Molecular and cellular biology High 16705185
2007 Depletion of THOC1 (pThoc1) selectively induces apoptotic cell death in neoplastic (oncogene-transformed) cells coincident with increased DNA damage (phospho-H2AX), while normal isogenic cells are largely unaffected; normal cells lacking Thoc1 cannot be transformed by E1A/Ha-ras. siRNA depletion, isogenic normal vs. oncogene-transformed cell comparison, apoptosis assay, γ-H2AX immunostaining, transformation assay Cancer research High 17638875
2005 Yeast Hpr1p (THOC1 ortholog) is poly-ubiquitinated by the HECT ubiquitin ligase Rsp5p (with Ubc4p as conjugating enzyme), leading to proteasomal degradation; Hpr1p degradation is enhanced at high temperature and linked to ongoing RNA Pol II transcription, while other THO subunits are unaffected, suggesting Hpr1p turnover controls THO/TREX complex formation and mRNA export. In vivo and in vitro ubiquitylation assays, genetic epistasis, proteasome inhibitor experiments, temperature-shift experiments The Journal of biological chemistry High 15713680
2013 Mammalian THOC1 protein is poly-ubiquitinated by the NEDD4-1 E3 ubiquitin ligase and degraded by the proteasome; destabilization of Thoc1 upon transcriptional elongation inhibitor treatment is NEDD4-1-dependent, indicating this regulation is evolutionarily conserved from yeast (Rsp5) to mammals. In vitro reconstituted ubiquitylation assay, molecularly manipulated cells (NEDD4-1 modulation), proteasome inhibitor treatment, immunoblot PloS one High 23460917
2007 The UBA domain of the mRNA export factor Mex67 directly interacts with Hpr1 (THOC1 ortholog), and this interaction is required for cotranscriptional recruitment of Mex67 to activated genes; Hpr1 binding modulates Mex67 UBA domain selectivity for polyubiquitin through a helix H4-dependent conformational switch. NMR structure of UBA-Mex67 domain, deletion/point mutagenesis, FRET-based binding assays, ChIP for cotranscriptional recruitment, in vivo mRNA export assay Molecular biology of the cell High 17475778
2009 Hpr1 and FXFG nucleoporin repeats bind to overlapping sites on the Mex67 UBA domain with analogous NMR chemical shift perturbations; Hpr1 binding (unlike FXFG binding) allows the UBA domain to interact with polyubiquitin, demonstrating that substrate identity controls ubiquitin affinity of the UBA domain. Solution NMR structure of UBA-Mex67/FXFG peptide complex, NMR titration with Hpr1, FRET-based binding assays The Journal of biological chemistry High 19401465
2014 Conditional deletion of Thoc1 in the hematopoietic system reveals a cell-autonomous requirement for THOC1 in granulocyte macrophage progenitor growth and viability, while lymphoid lineages are unaffected under homeostatic conditions, indicating THOC1 is selectively required in rapidly proliferating myeloid progenitors. Conditional/inducible Thoc1 knockout mice, bone marrow reconstitution, flow cytometry of hematopoietic lineages PloS one High 24830368
2014 Conditional Thoc1 deletion in an autochthonous mouse prostate cancer model prevents cancer progression but has little effect on normal prostate tissue; prostate cancer cells deprived of Thoc1 show gene expression defects that compromise cell growth, demonstrating THOC1 is required to support the gene expression demands of aggressive cancer. Conditional mouse knockout (Cre/lox), autochthonous prostate cancer mouse model, gene expression profiling Journal of the National Cancer Institute High 25296641
2007 Mice homozygous for a hypomorphic Thoc1 allele are viable but express reduced pThoc1 and exhibit a dwarf phenotype detectable from mid-gestation, indicating THOC1 is required for normal embryonic and postnatal development. Generation of hypomorphic and conditional Thoc1 alleles in mice, Cre-mediated recombination phenotyping, developmental staging Genesis (New York, N.Y. : 2000) High 17211872
2016 THOC1 is required to support increased E2F protein levels and expression of E2F-regulated apoptotic genes (Apaf1, Bak1) upon Rb1 loss; Thoc1 deficiency reduces apoptosis in the Rb1-null embryonic brain, placing THOC1 downstream of Rb1 in regulating E2F-dependent transcription of apoptotic regulators. Compound Rb1/Thoc1-hypomorphic mouse mutants, immunostaining for E2F and apoptotic markers, gene expression analysis of E2F targets Molecular and cellular biology High 27001308
2020 THOC1 deficiency in zebrafish causes hair cell apoptosis through the p53 signaling pathway; knockdown phenotype (reduced hair cell numbers, absent C-startle response) is rescued by wild-type human THOC1 mRNA but not by the p.L183V disease variant, and is suppressed by p53 depletion or the p53 inhibitor Pifithrin-α. CRISPR-Cas9 knockout and morpholino knockdown in zebrafish, behavioral testing (C-startle response), transcriptome sequencing, p53 inhibitor rescue, mRNA complementation with wild-type vs. mutant THOC1 PLoS genetics High 32776944
2013 Nitric oxide (NO) produced by activated macrophages suppresses THOC1 expression via Nrf2 binding to the antioxidant response element (ARE) in the THOC1 promoter; THOC1 downregulation is required for subsequent Bcl-2 suppression and cancer cell apoptosis, placing THOC1 in the NO-Nrf2-THOC1-Bcl2 apoptotic axis. Co-culture of macrophages with cancer cells, iNOS inhibitor rescue, NO donor treatment, promoter-reporter ARE mutation, Nrf2 overexpression/knockdown, immunoblot for Bcl-2 Biochemical pharmacology Medium 23688498
2006 An hpr1-101 point mutation (yeast THOC1 ortholog) impairs transcription and mRNA export without increasing recombination or retarding replication fork progression, and does not cause R-loop accumulation (as shown by AID-induced mutation pattern), demonstrating that THOC1/THO has a transcriptional function separable from R-loop-mediated genome instability. Site-directed mutagenesis, transcription elongation assays, mRNA export assays, recombination frequency measurement, DNA replication fork assay, AID-induced mutation spectrum analysis Molecular and cellular biology High 16908536 19451165
2020 THOC1 knockdown in hepatocellular carcinoma cells leads to R-loop formation and DNA damage, impairs G2/M cell cycle progression, and sensitizes cells to cisplatin; THOC1 promotes HCC proliferation in vivo. siRNA knockdown, R-loop detection (S9.6 antibody), DNA damage assay (γ-H2AX), cell cycle analysis, xenograft mouse model, colony formation assay Journal of experimental & clinical cancer research : CR Medium 32669125
2024 THOC1 interacts with SIN3A (a histone deacetylase complex component), and THOC1 knockdown leads to elevated R-loop levels (particularly at telomeres), reduced histone deacetylation, and shortened telomeres in glioblastoma cells, placing THOC1 in a SIN3A-dependent pathway that prevents telomeric R-loop accumulation. CRISPR-KO screen, co-immunoprecipitation of THOC1-SIN3A, R-loop detection (S9.6), ChIP for histone deacetylation marks, telomere length assay, RNA-sequencing, in vivo PDX survival model Neoplasia (New York, N.Y.) Medium 41496272
2025 THOC1 directly binds U2AF2 (U2 snRNA auxiliary factor 2) at the THOC1-340S interaction site; this interaction regulates U2AF2 expression and suppresses ovarian cancer cell proliferation, migration, and invasion through inhibition of the Wnt/beta-catenin signaling pathway (reduced cyclinD1, c-myc, beta-catenin). Co-immunoprecipitation, GST pull-down, immunofluorescence, RNA-seq with KEGG pathway analysis, functional cell assays (proliferation, migration, invasion) Cancer cell international Medium 41372894
2001 High-copy expression of Sub2p (yeast UAP56 homolog) suppresses hpr1Δ-mediated genome instability, and conversely high-copy HPR1 suppresses sub2 mutant instability, establishing a genetic epistatic relationship between THOC1 (Hpr1) and the RNA helicase Sub2/UAP56 in maintaining genome stability. Genetic suppressor analysis, high-copy suppression, conditional allele experiments in yeast Molecular and cellular biology Medium 11463828
2009 Hpr1 (THOC1 yeast ortholog) loss in cells lacking HPR1 results in increased levels of Nab2, Yra1, and Mex67 in nuclear mRNPs; overexpression of Nab2 or Yra1 suppresses the mRNA export defect of hpr1Δ cells and restores normal Mex67 levels in nuclear mRNPs, indicating THOC1/Hpr1 regulates the composition of nuclear mRNPs to permit efficient mRNA export. Genetic suppression, mRNP fractionation/immunoblot, mRNA export assay in yeast bioRxivpreprint Low bio_10.1101_2025.02.26.640412
2022 THOC1 promotes triple-negative breast cancer stem cell characteristics and mRNA export of stemness-related genes; THOC1 knockdown reduces mammosphere formation, CSC populations, and lung metastasis in vivo, while THOC1 overexpression promotes TNBC malignancy. NF-κB acts as an upstream transcriptional regulator of THOC1 expression. siRNA knockdown, stable overexpression, mammosphere assay, orthotopic mouse tumor model with lung metastasis readout, mRNA export assay for stemness genes, NF-κB reporter/inhibitor Biochemical pharmacology Medium 36330949

Source papers

Stage 0 corpus · 64 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Integrin-associated protein is a ligand for the P84 neural adhesion molecule. The Journal of biological chemistry 286 9872987
2000 A protein complex containing Tho2, Hpr1, Mft1 and a novel protein, Thp2, connects transcription elongation with mitotic recombination in Saccharomyces cerevisiae. The EMBO journal 257 11060033
1997 The yeast HPR1 gene has a functional role in transcriptional elongation that uncovers a novel source of genome instability. Genes & development 145 9407037
1996 Mutations in the RNA polymerase II transcription machinery suppress the hyperrecombination mutant hpr1 delta of Saccharomyces cerevisiae. Genetics 139 8849885
2005 p84, a new Gbetagamma-activated regulatory subunit of the type IB phosphoinositide 3-kinase p110gamma. Current biology : CB 137 15797027
1990 HPR1, a novel yeast gene that prevents intrachromosomal excision recombination, shows carboxy-terminal homology to the Saccharomyces cerevisiae TOP1 gene. Molecular and cellular biology 116 2181275
2001 Hpr1 is preferentially required for transcription of either long or G+C-rich DNA sequences in Saccharomyces cerevisiae. Molecular and cellular biology 99 11564888
2002 Cloning and characterization of the human heparanase-1 (HPR1) gene promoter: role of GA-binding protein and Sp1 in regulating HPR1 basal promoter activity. The Journal of biological chemistry 83 11779847
1990 Central nervous system antigen P84 can serve as a substrate for neurite outgrowth. Developmental biology 83 2303162
2010 The conserved RNA trafficking proteins HPR1 and TEX1 are involved in the production of endogenous and exogenous small interfering RNA in Arabidopsis. The Plant cell 77 20798330
1997 The murine P84 neural adhesion molecule is SHPS-1, a member of the phosphatase-binding protein family. The Journal of neuroscience : the official journal of the Society for Neuroscience 73 9348339
2011 Differential expression of THOC1 and ALY mRNP biogenesis/export factors in human cancers. BMC cancer 67 21329510
2005 The mRNA nuclear export factor Hpr1 is regulated by Rsp5-mediated ubiquitylation. The Journal of biological chemistry 62 15713680
2000 Expression of a synapse-associated membrane protein, P84/SHPS-1, and its ligand, IAP/CD47, in mouse retina. The Journal of comparative neurology 58 10602092
2001 High-copy-number expression of Sub2p, a member of the RNA helicase superfamily, suppresses hpr1-mediated genomic instability. Molecular and cellular biology 53 11463828
2005 Human hHpr1/p84/Thoc1 regulates transcriptional elongation and physically links RNA polymerase II and RNA processing factors. Molecular and cellular biology 52 15870275
1989 Genetic and molecular analysis of recombination events in Saccharomyces cerevisiae occurring in the presence of the hyper-recombination mutation hpr1. Genetics 48 2668113
2011 Differential roles for the p101 and p84 regulatory subunits of PI3Kγ in tumor growth and metastasis. Oncogene 47 21996737
2011 HPR1, a component of the THO/TREX complex, plays an important role in disease resistance and senescence in Arabidopsis. The Plant journal : for cell and molecular biology 47 22035198
2013 Inhibition of peroxisomal hydroxypyruvate reductase (HPR1) by tyrosine nitration. Biochimica et biophysica acta 46 23860243
1994 Characterization of mutations that suppress the temperature-sensitive growth of the hpr1 delta mutant of Saccharomyces cerevisiae. Genetics 44 7982575
2006 Thoc1/Hpr1/p84 is essential for early embryonic development in the mouse. Molecular and cellular biology 43 16705185
2010 Characterization of EMU, the Arabidopsis homolog of the yeast THO complex member HPR1. RNA (New York, N.Y.) 42 20668032
2007 Cancer cells and normal cells differ in their requirements for Thoc1. Cancer research 41 17638875
2020 Mutation of HPR1 encoding a component of the THO/TREX complex reduces STOP1 accumulation and aluminium resistance in Arabidopsis thaliana. The New phytologist 40 32406528
1993 Deamidation of HPr, a phosphocarrier protein of the phosphoenolpyruvate:sugar phosphotransferase system, involves asparagine 38 (HPr-1) and asparagine 12 (HPr-2) in isoaspartyl acid formation. The Journal of biological chemistry 39 8349654
1995 HPR1 encodes a global positive regulator of transcription in Saccharomyces cerevisiae. Molecular and cellular biology 38 7862161
1994 Increase in incidence of chromosome instability and non-conservative recombination between repeats in Saccharomyces cerevisiae hpr1 delta strains. Molecular & general genetics : MGG 36 7816031
2006 An hpr1 point mutation that impairs transcription and mRNP biogenesis without increasing recombination. Molecular and cellular biology 34 16908536
2020 Knockdown of THOC1 reduces the proliferation of hepatocellular carcinoma and increases the sensitivity to cisplatin. Journal of experimental & clinical cancer research : CR 32 32669125
2010 Role of the specific interaction of UL112-113 p84 with UL44 DNA polymerase processivity factor in promoting DNA replication of human cytomegalovirus. Journal of virology 31 20538862
1996 The yeast HRS1 gene encodes a polyglutamine-rich nuclear protein required for spontaneous and hpr1-induced deletions between direct repeats. Genetics 28 8849881
1996 Mutations in the yeast SRB2 general transcription factor suppress hpr1-induced recombination and show defects in DNA repair. Genetics 27 8844143
2007 Coordination of Hpr1 and ubiquitin binding by the UBA domain of the mRNA export factor Mex67. Molecular biology of the cell 23 17475778
2006 In vivo and in vitro degradation of heparan sulfate (HS) proteoglycans by HPR1 in pancreatic adenocarcinomas. Loss of cell surface HS suppresses fibroblast growth factor 2-mediated cell signaling and proliferation. The Journal of biological chemistry 23 17121850
2020 THOC1 deficiency leads to late-onset nonsyndromic hearing loss through p53-mediated hair cell apoptosis. PLoS genetics 22 32776944
2009 Structural requirements for the ubiquitin-associated domain of the mRNA export factor Mex67 to bind its specific targets, the transcription elongation THO complex component Hpr1 and nucleoporin FXFG repeats. The Journal of biological chemistry 21 19401465
1996 Mutations in GCR3, a gene involved in the expression of glycolytic genes in Saccharomyces cerevisiae, suppress the temperature-sensitive growth of hpr1 mutants. Genetics 21 8846890
1995 Isolation and genetic analysis of extragenic suppressors of the hyper-deletion phenotype of the Saccharomyces cerevisiae hpr1 delta mutation. Genetics 21 7705651
2020 Gβγ is a direct regulator of endogenous p101/p110γ and p84/p110γ PI3Kγ complexes in mouse neutrophils. Science signaling 18 33144519
2014 The Thoc1 ribonucleoprotein and prostate cancer progression. Journal of the National Cancer Institute 18 25296641
2002 Defective nucleotide excision repair in yeast hpr1 and tho2 mutants. Nucleic acids research 15 12000839
2022 HPR1 Is Required for High Light Intensity Induced Photorespiration in Arabidopsis thaliana. International journal of molecular sciences 14 35457261
2007 An allelic series for studying the mouse Thoc1 gene. Genesis (New York, N.Y. : 2000) 13 17211872
2023 Molecular basis for differential activation of p101 and p84 complexes of PI3Kγ by Ras and GPCRs. Cell reports 12 36842083
2022 Andrographolide suppresses the malignancy of triple-negative breast cancer by reducing THOC1-promoted cancer stem cell characteristics. Biochemical pharmacology 12 36330949
2020 PI3Kγ Regulatory Protein p84 Determines Mast Cell Sensitivity to Ras Inhibition-Moving Towards Cell Specific PI3K Targeting? Frontiers in immunology 12 33193405
2013 The suppression of thoc1 in cancer cell apoptosis mediated by activated macrophages is nitric oxide-dependent. Biochemical pharmacology 12 23688498
2014 Thoc1 inhibits cell growth via induction of cell cycle arrest and apoptosis in lung cancer cells. Molecular medicine reports 10 24682263
1997 Mapping of the human P84 gene to the subtelomeric region of chromosome 20p. Somatic cell and molecular genetics 9 9542532
2009 R-loops do not accumulate in transcription-defective hpr1-101 mutants: implications for the functional role of THO/TREX. Nucleic acids research 8 19451165
2015 p84 forms a negative regulatory complex with p110γ to control PI3Kγ signalling during cell migration. Immunology and cell biology 7 25753393
2016 Evaluating Effects of Hypomorphic Thoc1 Alleles on Embryonic Development in Rb1 Null Mice. Molecular and cellular biology 6 27001308
2014 The Thoc1 encoded ribonucleoprotein is required for myeloid progenitor cell homeostasis in the adult mouse. PloS one 6 24830368
2006 Combination gene therapy with p53 and Thoc1/p84 is more effective than either single agent in an animal model of human pancreatic adenocarcinoma. International journal of oncology 6 16465385
2004 Effects of mismatch repair and Hpr1 on transcription-stimulated mitotic recombination in the yeast Saccharomyces cerevisiae. DNA repair 5 15380099
2024 Specific Requirement of the p84/p110γ Complex of PI3Kγ for Antibody-Activated, Inducible Cross-Presentation in Murine Type 2 DCs. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 4 39382167
2019 Fabrication of Defect-Free P84® Polyimide Hollow Fiber for Gas Separation: Pathway to Formation of Optimized Structure. Membranes 3 31881799
2013 The Thoc1 encoded ribonucleoprotein is a substrate for the NEDD4-1 E3 ubiquitin protein ligase. PloS one 3 23460917
2024 THOC1 complexes with SIN3A to regulate R-loops and promote glioblastoma progression. bioRxiv : the preprint server for biology 1 39386597
2026 THOC1 complexes with SIN3A to regulate R-loops and promote glioblastoma progression. Neoplasia (New York, N.Y.) 0 41496272
2025 THOC1 binds to U2AF2 and regulates ovarian cancer progression through the beta-catenin / c-myc / cyclinD1 signaling pathway. Cancer cell international 0 41372894
2024 A patient with 18p11.32-p11.21 deletion have monaural deafness caused by an inadequate haplodose of THOC1: A case report. Medicine 0 39058882
2002 Fertility reduced by immunization with p84: A human sperm-coating antigen in the mouse. Reproductive medicine and biology 0 29699071