Affinage

UTP25

U3 small nucleolar RNA-associated protein 25 homolog · UniProt Q68CQ4

Length
756 aa
Mass
87.1 kDa
Annotated
2026-06-11
100 papers in source corpus 14 papers cited in narrative 14 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

UTP25 (also DEF/DIEXF) is a conserved nucleolar protein with dual roles: it is a component of the small subunit (SSU) processome required for 18S rRNA maturation, and it serves as a scaffold that recruits the cysteine protease CAPN3 to the nucleolus to drive a proteasome-independent protein degradation pathway (PMID:20884785, PMID:23357851, PMID:27657329). As an SSU processome subunit, Utp25 associates with U3 snoRNA, Mpp10, and the t-Utp/UtpA, UtpB, and U3 snoRNP subcomplexes, providing inter-subcomplex bridging connections; its depletion blocks pre-18S rRNA cleavage at sites A0, A1, and A2, and in human neuroblastoma cells its loss induces apoptosis (PMID:20884785, PMID:28263972). The protein directly binds CAPN3 through the C-terminal two-thirds of Def and an 86-residue motif (residues 430–515) in CAPN3, and determines the nucleolar localization of CAPN3, a step potentiated by simultaneous Def phosphorylation at S87 and S92 (PMID:27657329, PMID:35878425). Within the nucleolus, the Ca2+-dependent, proteasome-independent Def-CAPN3 complex degrades p53 (including several p53 mutants but not p53R175H), the processome component Mpp10, and the checkpoint proteins Chk1 and Wee1, coupling rRNA biogenesis to cell-cycle control (PMID:23357851, PMID:27657329, PMID:34452850). The pathway is essential for digestive organ development in zebrafish and for mammalian liver homeostasis and regeneration, where Def loss provokes inflammation, fibrosis, and impaired regeneration via a Def–p53–TGFβ axis (PMID:16322560, PMID:24801718, PMID:32303961). Homozygous Diexf deletion is embryonic lethal in mice, and this lethality is independent of p53, indicating an essential developmental role distinct from p53 regulation (PMID:29262616). DEF also binds the NF-κB subunit p65 to shield it from proteasomal degradation, a function exploited for tumor growth in pancreatic cancer (PMID:38757623).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2005 High

    Established that the gene is a digestive-organ growth factor acting through the p53 pathway, defining its physiological importance before its molecular activity was known.

    Evidence Zebrafish def loss-of-function mutant with p53-pathway epistasis and in situ hybridization

    PMID:16322560

    Open questions at the time
    • Molecular function of Def at the time undefined
    • How endoderm-restricted expression is achieved unknown
    • Mechanism linking Def loss to Delta113p53 upregulation not resolved
  2. 2010 High

    Defined the conserved molecular activity by showing the yeast ortholog is an SSU processome subunit required for 18S rRNA cleavage and providing the first inter-subcomplex connections within the processome.

    Evidence Yeast genetic depletion with Northern rRNA processing analysis, reciprocal Co-IP, two-hybrid, and domain mutagenesis

    PMID:20884785

    Open questions at the time
    • Putative helicase motif Ia found dispensable, leaving catalytic function unclear
    • Whether processome role connects to the vertebrate p53 phenotype not addressed
    • No structural model of subcomplex bridging
  3. 2013 High

    Explained how Def restrains p53 by identifying a novel nucleolar, proteasome-independent degradation pathway mediated by the protease CAPN3, and confirmed cell-autonomous liver function.

    Evidence Zebrafish loss-of-function, subcellular fractionation, proteasome-inhibitor controls, CAPN3 epistasis, and transgenic liver-specific rescue

    PMID:23357851 PMID:23593122

    Open questions at the time
    • Direct biochemical demonstration of CAPN3 cleavage of p53 not shown
    • Basis of organ-specific cell autonomy unexplained
    • How Def and CAPN3 are brought together unknown
  4. 2014 High

    Placed Def in a regeneration/fibrosis axis, showing Def–p53 signaling controls inflammatory resolution and scarring through TGFβ and HMGB1.

    Evidence Zebrafish haploinsufficiency with partial hepatectomy, p53 epistasis rescue, and pharmacological TGFβ/anti-inflammatory inhibitors

    PMID:24801718

    Open questions at the time
    • Direct molecular link from Def to HMGB1 not defined
    • Cell types driving fibrosis not dissected
    • Relevance to non-hepatic regeneration unclear
  5. 2016 High

    Resolved the mechanism of CAPN3 recruitment, showing Def binds CAPN3 directly and that phosphorylation at S87/S92 drives nucleolar CAPN3 localization required for p53 degradation and cell-cycle progression.

    Evidence Co-IP, phosphorylation-site mutagenesis with functional readouts, immunofluorescence/fractionation, and zebrafish genetics

    PMID:27657329

    Open questions at the time
    • Kinase responsible for S87/S92 phosphorylation not identified
    • Why p53R175H is resistant to degradation unexplained
    • Substrate specificity determinants unknown
  6. 2017 High

    Extended the processome role to vertebrates and oncogenesis, linking DEF dosage to MYCN-driven pre-rRNA pathway switching and neuroblastoma, and showed mouse Diexf is essential but p53-independent in development.

    Evidence Zebrafish genetics, transgenic neuroblastoma model, siRNA in human cells with pre-rRNA analysis, and knockout mice with p53 double-knockout epistasis and irradiation challenge

    PMID:28263972 PMID:29262616

    Open questions at the time
    • The p53-independent essential function in mice is undefined
    • Mechanism of MYCN-induced pathway switching unresolved
    • Reconciliation of p53-dependent zebrafish and p53-independent mouse phenotypes incomplete
  7. 2020 High

    Confirmed the mammalian liver requirement, showing hepatocyte-specific Def loss causes inflammation, biliary hyperplasia, and lethal failure of regeneration after hepatectomy.

    Evidence Conditional hepatocyte knockout mice with partial hepatectomy and dexamethasone rescue

    PMID:32303961

    Open questions at the time
    • Whether the liver phenotype depends on the CAPN3 or processome activity not separated
    • Molecular drivers of biliary hyperplasia unknown
  8. 2021 Medium

    Generalized the Def-CAPN3 pathway beyond p53, defining it as a Ca2+-dependent, proteasome-independent nucleolar turnover system for Mpp10, Chk1, and Wee1.

    Evidence Review synthesizing prior Co-IP, depletion, fractionation, and rescue data

    PMID:34452850

    Open questions at the time
    • Review, not new primary data
    • Direct cleavage of Chk1/Wee1/Mpp10 by CAPN3 not biochemically shown
    • How substrate selection is regulated unknown
  9. 2022 Medium

    Mapped the physical interface, identifying the CAPN3 residue 430–515 motif and the C-terminal two-thirds of Def as the interaction determinants conserved from fish to human.

    Evidence Truncation/internal-deletion mutagenesis and Co-IP domain mapping

    PMID:35878425

    Open questions at the time
    • Single method (Co-IP/deletion) without structural validation
    • Affinity and stoichiometry of the interaction not quantified
  10. 2024 Medium

    Identified a CAPN3-independent function, showing DEF binds p65 to protect it from proteasomal degradation and promote tumor growth, with a disruptive peptide as a therapeutic strategy.

    Evidence Reciprocal Co-IP, siRNA knockdown, in vitro/in vivo tumor assays, and peptide competition with modeling

    PMID:38757623

    Open questions at the time
    • Single lab; relevance to normal physiology unclear
    • Whether p65 binding occurs in nucleolus or cytoplasm not defined
    • Relationship to the processome and CAPN3 functions unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The p53-independent essential developmental function in mammals and the biochemical basis of CAPN3 substrate selection remain the central unresolved questions.
  • No direct reconstitution of CAPN3-mediated substrate cleavage
  • Kinase controlling Def S87/S92 phosphorylation unidentified
  • Mechanism uniting rRNA processing, protein degradation, and developmental essentiality unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0003723 RNA binding 2 GO:0140313 molecular sequestering activity 2
Localization
GO:0005730 nucleolus 4 GO:0005634 nucleus 2
Pathway
R-HSA-392499 Metabolism of proteins 3 R-HSA-1640170 Cell Cycle 2 R-HSA-8953854 Metabolism of RNA 2
Partners
CAPN3MPP10P53RELA
Complex memberships
SSU processome

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 Yeast Utp25 (YIL091C) is a component of the SSU processome; genetic depletion causes 18S rRNA maturation defects at sites A0, A1, and A2. Co-immunoprecipitation confirmed association with U3 snoRNA, Mpp10, and components of t-Utp/UtpA, UtpB, and U3 snoRNP subcomplexes. Two-hybrid screening identified interactions with Mpp10, Utp3, and Utp21, providing the first inter-subcomplex connections within the SSU processome. The C-terminal DUF1253 domain is required and sufficient for interaction with Utp3. Mutation of conserved motif Ia residues produced no growth defect, indicating this putative helicase motif is dispensable for function. Genetic depletion + Northern analysis, co-immunoprecipitation, yeast two-hybrid, domain truncation/mutagenesis RNA High 20884785
2005 Zebrafish def (digestive organ expansion factor) encodes a pan-endoderm-specific nuclear factor required for digestive organ growth. Loss-of-function of def selectively upregulates Delta113p53 expression within mutant digestive organs, triggering p53-responsive cell-cycle arrest (but not apoptosis), resulting in hypoplastic organs. Zebrafish loss-of-function mutant (defhi429), genetic epistasis with p53 pathway, in situ hybridization, cell-cycle analysis Genes & development High 16322560
2013 Def is a nucleolar protein; loss of def causes p53 protein to accumulate in nucleoli. Def mediates proteasome-independent degradation of p53 through the cysteine protease Calpain3 (CAPN3). This defines a novel nucleolar protein degradation pathway for p53 turnover. Zebrafish loss-of-function, subcellular fractionation/immunofluorescence, proteasome inhibitor controls, genetic epistasis with CAPN3, overexpression rescue Cell research High 23357851
2016 Def directly interacts with CAPN3 in the nucleolus and determines nucleolar localization of CAPN3, which is a prerequisite for p53 degradation there. Def is phosphorylated at five serine residues (S50, S58, S62, S87, S92); simultaneous phosphorylation at S87 and S92 facilitates nucleolar localization of CAPN3, which is essential for p53 degradation and cell-cycle progression. CAPN3 degrades wild-type p53 and mutants p53A138V, p53M237I, p53R248W, and p53R273P, but not p53R175H. Co-immunoprecipitation, site-directed mutagenesis of phosphorylation sites, subcellular localization (immunofluorescence/fractionation), zebrafish genetics, cell-cycle analysis PLoS biology High 27657329
2017 DEF functions in pre-rRNA processing as an SSU processome component in vivo. def-deficient zebrafish show underdeveloped peripheral sympathetic nervous system; def haploinsufficiency reduces disease penetrance and tumor growth in a MYCN-driven transgenic neuroblastoma model. MYCN overexpression shifts pre-rRNA processing from Pathway 1 to Pathway 2 (different temporal order of cleavages), and DEF depletion in human neuroblastoma cell lines induces apoptosis. Zebrafish loss-of-function genetics, transgenic neuroblastoma model, siRNA knockdown in human cell lines, Northern/pre-rRNA processing analysis Oncogene High 28263972
2014 Zebrafish def haploinsufficiency activates a p53-dependent TGFβ signaling pathway after partial hepatectomy, resulting in prolonged inflammatory response, impaired leukocyte clearance, and fibrotic scar formation at the amputation site. This phenotype was rescued by Def overexpression, p53 loss-of-function, anti-inflammatory dexamethasone, or TGFβ inhibitor SB431542. Def-p53 pathway suppresses fibrosis at least in part through regulation of HMGB1 (high-mobility group box 1). Zebrafish genetics (haploinsufficiency model), partial hepatectomy, genetic epistasis (p53 loss-of-function rescue), pharmacological inhibitors, molecular pathway analysis PloS one High 24801718
2013 Def functions cell-autonomously during liver development; transgenic liver-specific Def overexpression restores liver but not exocrine pancreas or intestine development in def mutant zebrafish, demonstrating organ-specific cell-autonomous function. Aberrant Def expression in adult liver disrupts intrahepatic structural integrity and alters specific functional pathways as shown by microarray analysis. Transgenic rescue (Tg(fabp10a:def)), zebrafish genetics, histology, microarray gene expression analysis PloS one Medium 23593122
2017 Homozygous deletion of mouse Diexf (UTP25/DEF) is embryonic lethal. Unlike Mdm2 and Mdm4 knockouts, loss of p53 does not rescue the Diexf embryonic lethal phenotype. Diexf heterozygous mice are not sensitized to sub-lethal ionizing radiation, indicating Diexf is an essential developmental gene in mammals but is NOT a significant regulator of the p53 pathway during mouse development or in response to ionizing radiation. Conditional and constitutive knockout mice, p53 double-knockout epistasis, ionizing radiation challenge Oncotarget High 29262616
2020 Conditional knockout of mouse def gene in hepatocytes causes cell morphology abnormalities, chronic inflammatory infiltration, multiple tissue damage foci, and biliary hyperplasia with age. Partial hepatectomy in def conditional knockout mice causes sudden acute death, rescued by pre-treatment with the anti-inflammation drug dexamethasone, demonstrating Def is essential for mammalian liver homeostasis and regeneration capacity. Conditional hepatocyte-specific knockout mice, partial hepatectomy, pharmacological rescue (dexamethasone), histology Science China. Life sciences High 32303961
2021 The nucleolus-localized Def-CAPN3 pathway controls turnover of multiple substrates including p53, SSU processome component Mpp10, and checkpoint proteins Chk1 and Wee1. CAPN3 is recruited by Def from the cytoplasm to the nucleolus; Def depletion excludes CAPN3 and causes accumulation of these substrates in the nucleolus, resulting in cell-cycle arrest and rRNA processing defects. This pathway is Ca2+-dependent and independent of the ubiquitin-proteasome pathway. Review synthesizing prior Co-IP, genetic depletion, subcellular fractionation, and functional rescue experiments from zebrafish and human cell studies Journal of genetics and genomics Medium 34452850
2022 An 86-amino acid motif (residues 430–515) in human CAPN3 is essential for its interaction with human Def (hDef). This motif is highly conserved in zebrafish Capn3b and is required for the zDef-zCapn3b interaction. The 2/3 C-terminus of hDef mediates the hDef-hCAPN3 interaction, and the corresponding region is conserved in zebrafish. Truncation and internal deletion mutagenesis of CAPN3, co-immunoprecipitation, domain mapping of Def Biochemical and biophysical research communications Medium 35878425
2024 DEF binds to p65 (NF-κB subunit) in cancer cells, shielding it from ubiquitin-proteasome-mediated degradation. DEF depletion impedes tumor growth in pancreatic cancer models in vitro and in vivo. A DEF-mimicking peptide (peptide-031) designed to disrupt the DEF-p65 interaction inhibits tumor proliferation in vitro and in vivo. Co-immunoprecipitation, siRNA knockdown, in vitro and in vivo tumor growth assays, peptide competition, computational modeling Advanced science Medium 38757623
2014 miR-195 down-regulates DIEXF (UTP25/DEF) in colon cells; increased miR-195 (as observed in Hirschsprung's disease tissues) suppresses DIEXF levels and impairs cell migration and proliferation in vitro. miRNA overexpression/inhibition in cell lines, Transwell migration assay, CCK-8 proliferation assay, qRT-PCR/Western blot BMC gastroenterology Low 25007945
2020 An Alu repeat element (AluSq2) with differential DNA methylation located upstream of the DIEXF promoter is associated with DIEXF transcript diversity and protein levels across normal and cancer tissues; alternate epigenetic profiles (DNA methylation and histone modifications) of AluSq2 correlate with DIEXF expression while the CpG island at the DIEXF promoter remains unchanged. Genome-wide DNA methylation analysis, chromatin immunoprecipitation (histone modifications), correlation of epigenetic state with DIEXF expression across cell types and cancers Epigenetics Low 32041475

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 ERK2 but not ERK1 induces epithelial-to-mesenchymal transformation via DEF motif-dependent signaling events. Molecular cell 261 20385094
2005 Loss of function of def selectively up-regulates Delta113p53 expression to arrest expansion growth of digestive organs in zebrafish. Genes & development 157 16322560
2012 Polycyclic aromatic hydrocarbons as skin carcinogens: comparison of benzo[a]pyrene, dibenzo[def,p]chrysene and three environmental mixtures in the FVB/N mouse. Toxicology and applied pharmacology 112 22935520
2004 Four DEF-like MADS box genes displayed distinct floral morphogenetic roles in Phalaenopsis orchid. Plant & cell physiology 110 15295066
2006 Analysis of the Petunia TM6 MADS box gene reveals functional divergence within the DEF/AP3 lineage. The Plant cell 104 16844905
2001 DEF-1/ASAP1 is a GTPase-activating protein (GAP) for ARF1 that enhances cell motility through a GAP-dependent mechanism. The Journal of biological chemistry 81 11773070
2008 Development of 3D PPF/DEF scaffolds using micro-stereolithography and surface modification. Journal of materials science. Materials in medicine 66 18763023
2013 Ribosome profiling: a Hi-Def monitor for protein synthesis at the genome-wide scale. Wiley interdisciplinary reviews. RNA 64 23696005
1999 A DEF/GLO-like MADS-box gene from a gymnosperm: Pinus radiata contains an ortholog of angiosperm B class floral homeotic genes. Developmental genetics 63 10528265
2013 Def defines a conserved nucleolar pathway that leads p53 to proteasome-independent degradation. Cell research 59 23357851
2007 A TAT-DEF-Elk-1 peptide regulates the cytonuclear trafficking of Elk-1 and controls cytoskeleton dynamics. The Journal of neuroscience : the official journal of the Society for Neuroscience 58 18160653
1999 Def-2, -3, -6 and -8, novel mouse genes differentially expressed in the haemopoietic system. British journal of haematology 51 10460589
2012 Sirt1: def-eating senescence? Cell cycle (Georgetown, Tex.) 49 22983125
1994 The DEF data base of sequence based protein fold class predictions. Nucleic acids research 49 7937069
2010 The DEAD-box RNA helicase-like Utp25 is an SSU processome component. RNA (New York, N.Y.) 44 20884785
2005 Identification of a DEF-type docking domain for extracellular signal-regulated kinases 1/2 that directs phosphorylation and turnover of the BH3-only protein BimEL. The Journal of biological chemistry 42 15728578
2014 DEF- and GLO-like proteins may have lost most of their interaction partners during angiosperm evolution. Annals of botany 41 24902716
1999 DEF-3(g16/NY-LU-12), an RNA binding protein from the 3p21.3 homozygous deletion region in SCLC. Oncogene 41 10353602
1995 The mechanism of recA polA lethality: suppression by RecA-independent recombination repair activated by the lexA(Def) mutation in Escherichia coli. Genetics 41 7789754
1974 "Alpha chain disease" protein def: internal deletion of a human immunoglobulin A1 heavy chain. Proceedings of the National Academy of Sciences of the United States of America 39 4595579
1999 DEF-1, a novel Src SH3 binding protein that promotes adipogenesis in fibroblastic cell lines. Molecular and cellular biology 35 10022919
2004 Purine nucleoside phosphorylase deficiency (PNP-def) presenting with lymphopenia and developmental delay: successful correction with umbilical cord blood transplantation. The Journal of pediatrics 34 15520787
2016 Phosphorylation of Def Regulates Nucleolar p53 Turnover and Cell Cycle Progression through Def Recruitment of Calpain3. PLoS biology 31 27657329
2007 Def-6, a guanine nucleotide exchange factor for Rac1, interacts with the skeletal muscle integrin chain alpha7A and influences myoblast differentiation. The Journal of biological chemistry 30 17403664
2004 A Highly Abbreviated Synthesis of Dibenzo[def,p]chrysene and Its 12-Methoxy Derivative, a Key Precursor for the Synthesis of the Proximate and Ultimate Carcinogens of Dibenzo[def,p]chrysene. The Journal of organic chemistry 29 15153038
2019 Comparative mechanisms of PAH toxicity by benzo[a]pyrene and dibenzo[def,p]chrysene in primary human bronchial epithelial cells cultured at air-liquid interface. Toxicology and applied pharmacology 28 31255691
2017 The pre-rRNA processing factor DEF is rate limiting for the pathogenesis of MYCN-driven neuroblastoma. Oncogene 28 28263972
1997 Enhanced generation of A:T-->T:A transversions in a recA730 lexA51(Def) mutant of Escherichia coli. Mutation research 28 9015154
2014 In vitro metabolism of benzo[a]pyrene and dibenzo[def,p]chrysene in rodent and human hepatic microsomes. Toxicology letters 27 24769260
2017 Hypomethylated Fgf3 is a potential biomarker for early detection of oral cancer in mice treated with the tobacco carcinogen dibenzo[def,p]chrysene. PloS one 26 29073177
2014 Haploinsufficiency of Def activates p53-dependent TGFβ signalling and causes scar formation after partial hepatectomy. PloS one 26 24801718
2017 In vitro metabolism of benzo[a]pyrene-7,8-dihydrodiol and dibenzo[def,p]chrysene-11,12 diol in rodent and human hepatic microsomes. Toxicology letters 24 28119020
1990 Genetic analysis of the LexA repressor: isolation and characterization of LexA(Def) mutant proteins. Molecular & general genetics : MGG 24 2259342
2014 The analysis of the inflorescence miRNome of the orchid Orchis italica reveals a DEF-like MADS-box gene as a new miRNA target. PloS one 23 24832004
2014 MiR-195 affects cell migration and cell proliferation by down-regulating DIEXF in Hirschsprung's disease. BMC gastroenterology 23 25007945
1986 Antioxidant enzyme activities and malondialdehyde, glutathione and methemoglobin concentrations in channel catfish exposed to DEF and n-butyl mercaptan. Comparative biochemistry and physiology. C, Comparative pharmacology and toxicology 22 2879702
2020 Role of a DEF/Y motif in histone H2A-H2B recognition and nucleosome editing. Proceedings of the National Academy of Sciences of the United States of America 21 32001508
2013 Impact of pregnancy on the pharmacokinetics of dibenzo[def,p]chrysene in mice. Toxicological sciences : an official journal of the Society of Toxicology 21 23744095
2006 Phylogenetic utility of the AP3/DEF K-domain and its molecular evolution in Impatiens (Balsaminaceae). Molecular phylogenetics and evolution 20 17254808
2021 A viroporin-like 2B protein of duck hepatitis A virus 1 that induces incomplete autophagy in DEF cells. Poultry science 19 34403988
2018 Involvement of the def-1 Mutation in the Response of Tomato Plants to Arbuscular Mycorrhizal Symbiosis Under Well-Watered and Drought Conditions. Plant & cell physiology 19 29165704
2013 DEF pocket in p38α facilitates substrate selectivity and mediates autophosphorylation. The Journal of biological chemistry 19 23671282
1984 Induction of hepatic microsomal cytochrome P-450 and inhibition of brain, liver, and plasma esterases by an acute dose of S,S,S-tri-n-butyl phosphorotrithioate (DEF) in the adult hen. Toxicology and applied pharmacology 19 6710530
2020 Black Raspberry Inhibits Oral Tumors in Mice Treated with the Tobacco Smoke Constituent Dibenzo(def,p)chrysene Via Genetic and Epigenetic Alterations. Cancer prevention research (Philadelphia, Pa.) 18 31969344
2015 Tissue Distribution, Excretion and Pharmacokinetics of the Environmental Pollutant Dibenzo[def,p]chrysene in Mice. Chemical research in toxicology 18 26034881
2013 Differential modulation of dibenzo[def,p]chrysene transplacental carcinogenesis: maternal diets rich in indole-3-carbinol versus sulforaphane. Toxicology and applied pharmacology 18 23566957
1985 Weigle reactivation and mutagenesis of bacteriophage lambda in lexA(Def) mutants of E. coli K12. Molecular & general genetics : MGG 18 2935711
2022 Detection of DNA adducts derived from the tobacco carcinogens, benzo[a]pyrene and dibenzo[def,p]chrysene in human oral buccal cells. Carcinogenesis 17 35749296
2010 Active mutants of the TCR-mediated p38α alternative activation site show changes in the phosphorylation lip and DEF site formation. Journal of molecular biology 17 21146537
1993 Characterization of dinY, a new Escherichia coli DNA repair gene whose products are damage inducible even in a lexA(Def) background. Journal of bacteriology 17 8423139
2020 DEF Cell-Derived Exosomal miR-148a-5p Promotes DTMUV Replication by Negative Regulating TLR3 Expression. Viruses 16 31947624
2020 Ribosome biogenesis gene DEF/UTP25 is essential for liver homeostasis and regeneration. Science China. Life sciences 15 32303961
2019 Duck Plague Virus Promotes DEF Cell Apoptosis by Activating Caspases, Increasing Intracellular ROS Levels and Inducing Cell Cycle S-Phase Arrest. Viruses 15 30813500
2004 Tumor formation in the neonatal mouse bioassay indicates that the potent carcinogen dibenzo[def,p]chrysene (dibenzo[a,l]pyrene) is activated in vivo via its trans-11,12-dihydrodiol. Chemico-biological interactions 15 15223354
1985 Effect of a lexA41(Ts) mutation on DNA repair in recA(Def) derivatives of Escherichia coli K-12. Molecular & general genetics : MGG 14 3911024
2019 Quantitative Proteomic Analysis Uncovers the Mediation of Endoplasmic Reticulum Stress-Induced Autophagy in DHAV-1-Infected DEF Cells. International journal of molecular sciences 13 31817666
2011 Characterization of dibenzo[a,l]pyrene-trans-11,12-diol (dibenzo[def,p]chrysene) glucuronidation by UDP-glucuronosyltransferases. Chemical research in toxicology 13 21780761
2007 Reduced susceptibility of Haemophilus influenzae to the peptide deformylase inhibitor LBM415 can result from target protein overexpression due to amplified chromosomal def gene copy number. Antimicrobial agents and chemotherapy 12 17220413
1998 Metabolic activation of racemic and enantiomeric trans-8, 9-dihydroxy-8,9-dihydrodibenzo[a,l]pyrene (dibenzo[def,p]chrysene) to dibenzo[a,l]pyrene-bis-dihydrodiols by induced rat liver microsomes and a recombinant human P450 1A1 system: the role of the K-region-derived metabolic intermediates in the formation of dibenzo[a,l]pyrene-DNA adducts. Chemical research in toxicology 12 9860506
2015 Transcriptional Profiling of Dibenzo[def,p]chrysene-induced Spleen Atrophy Provides Mechanistic Insights into its Immunotoxicity in MutaMouse. Toxicological sciences : an official journal of the Society of Toxicology 11 26496743
2013 Def functions as a cell autonomous factor in organogenesis of digestive organs in zebrafish. PloS one 11 23593122
2009 Effect of the DEF motif on phosphorylation of peptide substrates by ERK. Biochemical and biophysical research communications 11 19615338
2020 The environmental pollutant and tobacco smoke constituent dibenzo[def,p]chrysene is a co-factor for malignant progression of mouse oral papillomavirus infections. Chemico-biological interactions 10 33186600
2018 Virulent duck enteritis virus infected DEF cells generate a unique pattern of viral microRNAs and a novel set of host microRNAs. BMC veterinary research 10 29704894
2017 Loss of digestive organ expansion factor (Diexf) reveals an essential role during murine embryonic development that is independent of p53. Oncotarget 10 29262616
2008 Selection on length mutations after frameshift can explain the origin and retention of the AP3/DEF-like paralogues in Impatiens. Journal of molecular evolution 10 18392761
1986 Base pair substitution and frameshift mutagenesis induced by apurinic sites and two fluorene derivatives in a recA441 lexA (Def) strain. Molecular & general genetics : MGG 10 3515130
2021 Nucleolus-localized Def-CAPN3 protein degradation pathway and its role in cell cycle control and ribosome biogenesis. Journal of genetics and genomics = Yi chuan xue bao 9 34452850
2018 Alpha-defensins (α-Defs) in Crohn's disease: decrease of ileal α-Def 5 via permanent methylation and increase in plasma α-Def 1-3 concentrations offering biomarker utility. Clinical and experimental immunology 9 29193023
2013 Def-6, a novel regulator of small GTPases in podocytes, acts downstream of atypical protein kinase C (aPKC) λ/ι. The American journal of pathology 9 24096077
2002 Microsomal activation of dibenzo[def,mno]chrysene (anthanthrene), a hexacyclic aromatic hydrocarbon without a bay-region, to mutagenic metabolites. Chemical research in toxicology 9 11896680
2019 Heparin sulfate is the attachment factor of duck Tembus virus on both BHK21 and DEF cells. Virology journal 8 31718685
2015 Analysis of dibenzo[def,p]chrysene-deoxyadenosine adducts in wild-type and cytochrome P450 1b1 knockout mice using stable-isotope dilution UHPLC-MS/MS. Mutation research. Genetic toxicology and environmental mutagenesis 8 25868132
2013 Dibenzo[def,p]chrysene (DBC) suppresses antibody formation in spleen cells following oral exposures of mice. Journal of toxicology and environmental health. Part A 8 23151208
2003 Identification of AFLP and STS markers closely linked to the def locus in pea. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 8 12748781
2022 Black Raspberry Extract Enhances Glutathione Conjugation of the Fjord-Region Diol Epoxide Derived from the Tobacco Carcinogen Dibenzo[def,p]chrysene in Human Oral Cells. Chemical research in toxicology 7 36260657
2016 Dibenzo[def,p]chrysene transplacental carcinogenesis in wild-type, Cyp1b1 knockout, and CYP1B1 humanized mice. Molecular carcinogenesis 7 26990437
2009 Characterization and structural analysis of wild type and a non-abscission mutant at the development funiculus (Def) locus in Pisum sativum L. BMC plant biology 7 19549315
2020 Tissue and cancer-specific expression of DIEXF is epigenetically mediated by an Alu repeat. Epigenetics 6 32041475
2016 Immunolocalization of pectic polysaccharides during abscission in pea seeds (Pisum sativum L.) and in abscission less def pea mutant seeds. BMC research notes 6 27581466
2015 The influence of ATM, ATR, DNA-PK inhibitors on the cytotoxic and genotoxic effects of dibenzo[def,p]chrysene on human hepatocellular cancer cell line HepG2. Mutation research. Genetic toxicology and environmental mutagenesis 6 26338538
2024 Inhibition of DEF-p65 Interactions as a Potential Avenue to Suppress Tumor Growth in Pancreatic Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 5 38757623
2008 Synthesis of dibenzo[def,p]chrysene, its active metabolites, and their 13C-labeled analogues. Organic letters 5 18284245
1997 An update of the DEF database of protein fold class predictions. Nucleic acids research 5 9016543
2024 Cognitive impairment in Huntington's disease and its impact on functioning: Concept elicitation and cognitive debriefing for the Huntington's Disease Everyday Functioning (Hi-DEF) scale. Journal of Huntington's disease 4 39973381
2019 Peptide Deformylase (def) is essential in Mycobacterium smegmatis, but the essentiality is compensated by inactivation of methionine formylation. BMC microbiology 4 31655553
2018 Comparative Tumorigenicity and DNA Damage Induced by Dibenzo[ def,p]chrysene and Its Metabolites in the Mouse Ovary. Chemical research in toxicology 4 30260214
2000 H2O2-induced cross-protection against UV-C killing in Escherichia coli is blocked in a lexA (Def) background. Journal of photochemistry and photobiology. B, Biology 4 10739145
2024 Gender Difference in DNA Damage Induced by the Environmental Carcinogen Dibenzo[def,p]chrysene Individually and in Combination with Mouse Papillomavirus Infection in the Mouse Oral Cavity. ACS omega 3 38405470
2018 Long-lasting Corolla Cultivars in Japanese Azaleas: A Mutant AP3/DEF Homolog Identified in Traditional Azalea Cultivars from More Than 300 Years Ago. Frontiers in plant science 3 29375608
2016 DeF-GPU: Efficient and effective deletions finding in hepatitis B viral genomic DNA using a GPU architecture. Methods (San Diego, Calif.) 3 27480381
2024 Azole resistance screening in Aspergillus fumigatus sensu stricto using the azole-containing agar method (EUCAST E.Def 10.2): conidial suspension filtration and inoculum adjustment before inoculum preparation may not be needed. Journal of clinical microbiology 2 38819167
2024 Metabolic reprogramming in saliva of mice treated with the environmental and tobacco carcinogen dibenzo[def, p]chrysene. Scientific reports 2 39604478
2022 Screening of azole resistance in Aspergillus fumigatus using the EUCAST E.Def 10.2 azole-containing agar method: a single study suggests that filtration of conidial suspensions prior to inoculum preparation may not be needed. Mycoses 2 35796747
2022 An 86 amino acids motif in CAPN3 is essential for formation of the nucleolus-localized Def-CAPN3 complex. Biochemical and biophysical research communications 2 35878425
2019 The effect of inhibitors of phosphatidylinositol 3-kinase-related kinases on dibenzo[def,p]chrysene genotoxicity measured by γH2AX levels and neutral comet assay in HepG2 human hepatocellular cancer cells. Toxicology in vitro : an international journal published in association with BIBRA 2 31838185
2013 Fused polypeptide with DEF induces apoptosis of lung adenocarcinoma cells. Asian Pacific journal of cancer prevention : APJCP 2 24460299
2011 Growth, seed development and genetic analysis in wild type and Def mutant of Pisum sativum L. BMC research notes 2 22078070
1999 Metabolic activation of 4H-cyclopenta[def]chrysene in human mammary carcinoma MCF-7 cell cultures. Chemical research in toxicology 2 10328754
2024 Host miRNA and mRNA profiles during in DEF and duck after DHAV-1 infection. Scientific reports 1 39343789

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