Affinage

DEK

Protein DEK · UniProt P35659

Length
375 aa
Mass
42.7 kDa
Annotated
2026-06-09
100 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DEK is an abundant chromatin architectural protein that binds DNA non-sequence-specifically through two DNA-binding domains—one containing a SAF-box (aa 87–187) and a second (aa 270–350) overlapping a multimerization domain—and introduces positive supercoils into protein-free and chromatinized DNA, with flanking regions outside the SAF-box required for the positive (versus negative) topology change (PMID:11997399, PMID:15199153, PMID:15722484). DEK preferentially recognizes supercoiled and four-way junction DNA and modulates the activity of topoisomerase II and DNA ligase, consistent with a role in organizing higher-order chromatin structure (PMID:14627833). Its chromatin activity is tuned by post-translational modification: CK2 phosphorylation weakens DNA binding while phosphorylated DEK remains tethered via unphosphorylated DEK and drives multimerization (PMID:15199154, PMID:15199153), N-terminal acetylation by PCAF/p300 lowers DNA affinity and redistributes DEK to interchromatin granule clusters (PMID:15987677), and PARP1-mediated poly(ADP-ribosyl)ation, opposed by the histone chaperone SET, evicts DEK from chromatin to license RNA Pol II transcription (PMID:17529993). DEK enforces a repressive, compact chromatin state by inhibiting p300/PCAF histone acetyltransferase activity (PMID:16696975), directly binding HP1α to enhance its association with H3K9me3 and maintain heterochromatin integrity (PMID:21460035), and governing HIRA- and DAXX/ATRX-dependent deposition of histone variant H3.3 at telomeres and chromatin (PMID:25049225). DEK is required for genome stability, promoting both non-homologous end joining and homologous recombination—where it forms a complex with RAD51 and supports RAD51 filament formation—and facilitating replication fork progression under stress (PMID:21653549, PMID:25347734, PMID:28317934). In hematopoiesis, nuclear DEK partners with C/EBPα to drive granulocytic differentiation (PMID:22474248) and recruits the corepressor NCoR1 to restrict chromatin accessibility and H3K27 acetylation, maintaining HSC quiescence and self-renewal in part by restraining mTOR signaling (PMID:33755722). DEK also has an extracellular life: it is actively secreted by macrophages in free and exosomal forms in a CK2- and IL-8-dependent manner, acts as a chemoattractant and a CXCR2/heparan-sulfate-dependent hematopoietic cytokine, and can be re-internalized in a heparan-sulfate-dependent manner to rescue nuclear functions including heterochromatin integrity and DNA repair (PMID:17030615, PMID:23569252, PMID:31107242, PMID:21943234). DEK is recurrently exploited in cancer, where it sustains anti-apoptotic and oncogenic programs (MCL-1, ΔNp63, HIF-1α/VEGF, Wnt/β-catenin) and, as the DEK-NUP214 fusion, activates mTORC1 (PMID:19679545, PMID:26988756, PMID:24608431, PMID:24073922).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2002 High

    Establishing DEK's core biochemical activity: it was unknown how this abundant nuclear protein acts on DNA, and reconstitution showed it is a chromatin architectural factor that reversibly remodels DNA topology.

    Evidence In vitro supercoiling, band-shift, electron microscopy and sedimentation on protein-free and chromatin DNA

    PMID:11997399

    Open questions at the time
    • Did not define the domains responsible
    • No in vivo demonstration that topology change occurs at endogenous loci
  2. 2001 High

    Localizing DEK function to chromatin in cells, showing most cellular DEK is chromatin-bound across active and inactive fractions throughout the cell cycle.

    Evidence Cell fractionation, micrococcal nuclease digestion, glycerol gradient co-sedimentation with oligonucleosomes

    PMID:11333257

    Open questions at the time
    • Did not resolve sequence or structural determinants of binding
    • No functional consequence assigned
  3. 2003 High

    Defining DEK's substrate preference: it binds supercoiled and cruciform DNA non-sequence-specifically and cooperates with topoisomerase II and ligase, linking it to DNA topology management.

    Evidence Filter binding, band-shift, in vitro catenation and ligation assays

    PMID:14627833

    Open questions at the time
    • Physiological relevance of catenation/ligation stimulation unclear
    • No structural model of junction recognition
  4. 2004 High

    Mapping the molecular architecture and its regulation: two DNA-binding domains were defined and CK2 phosphorylation was shown to weaken DNA binding while controlling multimerization, providing a switch for DEK chromatin activity.

    Evidence Yeast two-hybrid, truncation/mutational analysis, in vitro supercoiling, kinase assay and MS site mapping

    PMID:15199153 PMID:15199154

    Open questions at the time
    • Cell-cycle role of CK2-regulated multimerization not functionally resolved
    • Subsequent truncation work showed fragments give negative supercoils, complicating domain assignment
  5. 2005 High

    Resolving which regions confer positive supercoiling, showing the SAF-box alone is insufficient and flanking sequences dictate the sign of topology change, and that N-terminal acetylation reroutes DEK to RNA-processing IGCs.

    Evidence Systematic truncation supercoiling assays; in vivo acetylation, DNA-binding, immunofluorescence with PCAF overexpression and inhibitor

    PMID:15722484 PMID:15987677

    Open questions at the time
    • Functional role of DEK at IGCs not defined
    • Acetyltransferase responsible in vivo not fully resolved
  6. 2006 Medium

    Connecting DEK to transcriptional repression via chromatin compaction by showing it inhibits p300/PCAF HAT activity and correlates with promoter histone hypoacetylation, and identifying upstream transcriptional control of DEK itself.

    Evidence Co-IP, in vitro HAT inhibition, ChIP; promoter-reporter mutagenesis and EMSA for E2F, NF-Y and YY1

    PMID:12483538 PMID:16696975 PMID:16721057

    Open questions at the time
    • Direct vs indirect HAT inhibition mechanism unclear
    • Single-lab ChIP for repression
  7. 2007 High

    Establishing the eviction logic for transcription: DEK must be removed from chromatin—by SET or by PARP1-mediated PARylation—to permit Mediator loading and Pol II transcription, defining DEK as a transcriptional gatekeeper.

    Evidence In vitro chromatin transcription reconstitution, nuclease accessibility, Mediator recruitment, SET/PARP1-resistant DEK variant

    PMID:17529993

    Open questions at the time
    • In vivo generality across promoters not established
    • Interplay with acetylation-driven eviction not integrated
  8. 2006 High

    Revealing an unexpected extracellular role: DEK is actively secreted by macrophages in free and exosomal forms and functions as a chemoattractant, expanding DEK beyond the nucleus.

    Evidence ELISA, exosome isolation, chemotaxis assays, pharmacologic modulation (IL-8, CK2, dexamethasone)

    PMID:17030615

    Open questions at the time
    • Secretion mechanism (unconventional pathway) not defined
    • Receptor for chemotactic activity not yet identified
  9. 2008 High

    Linking DEK PTMs to cell fate and autoimmunity: apoptotic PARylation/phosphorylation drive DEK release, and DEK protects cells from genotoxic stress while modified DEK becomes an autoantigen.

    Evidence In vivo modification analysis, DEK knockdown, DNA damage/viability assays, JIA autoantibody binding

    PMID:18332104

    Open questions at the time
    • Direct repair step DEK acts in not yet defined here
    • Causal role of release vs modification unresolved
  10. 2011 High

    Defining DEK as a heterochromatin maintenance factor through a direct HP1α interaction that enhances HP1α–H3K9me3 binding, with loss causing genome-wide heterochromatin reduction.

    Evidence Direct interaction assay, Drosophila Su(var) genetic screen, heterochromatin marker imaging, knockout analysis

    PMID:21460035

    Open questions at the time
    • Structural basis of DEK-HP1α enhancement unknown
    • Relationship to DEK topology activity not integrated
  11. 2011 High

    Establishing DEK's requirement in DNA double-strand break repair, with knockout cells defective in NHEJ and showing altered ATM/DNA-PK signaling.

    Evidence Knockdown and KO MEFs, γH2AX/FANCD2 staining, NHEJ reporter, kinase pathway analysis, xenografts

    PMID:21653549

    Open questions at the time
    • Molecular role of DEK within the NHEJ machinery not defined
    • Did not address HR contribution
  12. 2011 High

    Defining DEK's hematopoietic regulatory role both as intracellular factor and secreted protein, positively regulating HSC engraftment while directly inhibiting progenitor colony formation.

    Evidence Dek KO mice, recombinant protein treatment, colony assays, competitive transplantation

    PMID:21943234

    Open questions at the time
    • Receptor mediating recombinant DEK inhibition not yet identified
    • Mechanism distinguishing HSC vs HPC effects unresolved
  13. 2012 High

    Mechanistically linking DEK to granulopoiesis by identifying it as a chromatin partner of C/EBPα recruited to granulocytic target promoters.

    Evidence Immuno-affinity MS interactome, ChIP, DEK depletion, CD34+ differentiation assay

    PMID:22474248

    Open questions at the time
    • Whether DEK acts via topology or HP1/HAT inhibition at these promoters unclear
    • Single-lab finding
  14. 2013 High

    Demonstrating that secreted DEK is functional non-cell-autonomously: it is taken up via heparan sulfate, enters the nucleus, and rescues heterochromatin and repair defects in DEK-deficient cells.

    Evidence Live imaging, heparan sulfate inhibitors, knockdown rescue, heterochromatin marker staining

    PMID:23569252

    Open questions at the time
    • Endocytic route and nuclear import machinery not defined
    • Physiological extent of paraclrine rescue in vivo unclear
  15. 2014 High

    Extending DEK's chromatin role to histone variant management, controlling HIRA- and DAXX/ATRX-dependent H3.3 distribution and protecting telomere integrity.

    Evidence Live imaging, ChIP, immunofluorescence, depletion in somatic and ES cells, telomere FISH

    PMID:25049225

    Open questions at the time
    • Direct biochemical link between DEK and H3.3 chaperones not established
    • Mechanism of fragile telomere induction unresolved
  16. 2017 High

    Defining DEK's role in homologous recombination by showing it complexes with RAD51 and is required for RAD51 filament formation, with synthetic lethality between DEK loss and NHEJ inhibition.

    Evidence HR reporter assays, RAD51 foci, DEK-RAD51 Co-IP, KO mouse class-switch assay, NHEJ inhibitor sensitivity

    PMID:28317934

    Open questions at the time
    • How DEK promotes RAD51 loading mechanistically unknown
    • Reciprocal validation of complex limited to single lab
  17. 2019 High

    Separating DEK's extracellular cytokine activity from its nuclear function, showing recombinant DEK expands HSCs via CXCR2 and HSPGs through ERK/AKT/p38, independent of DNA binding or nuclear import.

    Evidence Recombinant DEK, Cxcr2-/- mice, blocking antibodies, HSPG inhibitors, transplantation, DEK domain mutants

    PMID:31107242

    Open questions at the time
    • Structural basis of DEK-CXCR2 engagement undefined
    • Relationship to colony inhibition reported earlier not fully reconciled
  18. 2021 High

    Mechanizing DEK's nuclear control of HSC quiescence by showing it recruits NCoR1 to repress H3K27ac and restrict chromatin accessibility, restraining mTOR signaling.

    Evidence Conditional DEK KO, ATAC-seq, H3K27ac ChIP-seq, DEK-NCoR1 Co-IP, mTOR inhibitor rescue, transplantation

    PMID:33755722

    Open questions at the time
    • Direct genomic co-occupancy of DEK and NCoR1 not mapped
    • Connection to topology/HP1 activities unresolved
  19. 2020 Medium

    Implicating phospho-DEK in post-transcriptional control of stem cell fate by modulating intron retention during satellite cell quiescence exit.

    Evidence RNA-seq of satellite cells, in vivo Dek overexpression, muscle regeneration assay

    PMID:32502396

    Open questions at the time
    • Direct splicing-machinery interaction not demonstrated
    • How a chromatin protein influences IR mechanistically unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DEK's biochemical activities (topology, HP1α/heterochromatin, HAT inhibition, H3.3 routing, RAD51-mediated HR) are mechanistically unified at the molecular level, and how PTM-driven eviction is coordinated in vivo across these functions, remains unresolved.
  • No structural model linking DNA topology activity to chromatin-factor recruitment
  • Unconventional secretion and endocytic uptake pathways undefined
  • Integration of nuclear vs extracellular DEK roles in vivo incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 4 GO:0140110 transcription regulator activity 4 GO:0042393 histone binding 3 GO:0048018 receptor ligand activity 3 GO:0005198 structural molecule activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005576 extracellular region 3 GO:0005634 nucleus 3 GO:0005694 chromosome 3 GO:0005654 nucleoplasm 2 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-4839726 Chromatin organization 4 R-HSA-168256 Immune System 3 R-HSA-73894 DNA Repair 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
CEBPAFBXW7HIF1AHP1ANCOR1PARP1RAD51SET

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 DEK induces positive supercoils into both protein-free DNA and chromatin DNA in vitro, causing intra- and intermolecular DNA interactions and distinct structural changes to chromatin, as demonstrated by band-shift assays and electron microscopy. The topology change is reversible upon DEK removal. Band-shift assays, electron microscopy, sedimentation analysis, in vitro supercoiling assay The Journal of biological chemistry High 11997399
2001 The majority of cellular DEK protein is associated with chromatin in vivo (released by DNase treatment), co-sedimenting with oligonucleosomes in glycerol gradients; DEK is present on both active and inactive chromatin fractions throughout the cell cycle. Cell fractionation, immunolabeling, micrococcal nuclease digestion, glycerol gradient sedimentation The Journal of biological chemistry High 11333257
2004 DEK is phosphorylated by protein kinase CK2 in vitro and in vivo; phosphorylation sites cluster in the C-terminal region (mapped by mass spectrometry); CK2 phosphorylation weakens DEK binding to DNA, yet phosphorylated DEK remains tethered to chromatin by unphosphorylated DEK. Phosphorylation fluctuates during the cell cycle with a moderate peak in G1. In vitro kinase assay, quadrupole ion trap mass spectrometry, filter binding assay, Southwestern analysis, cell cycle synchronization Molecular and cellular biology High 15199154
2004 DEK contains two DNA-binding domains: one spanning amino acids 87–187 (including the SAF-box, aa 149–187) sufficient to introduce supercoils, and a second at aa 270–350 that overlaps a multimerization domain. DEK multimerization is dependent on CK2 phosphorylation in vitro. Yeast two-hybrid screen, mutational analysis, in vitro supercoiling assay Molecular and cellular biology High 15199153
2003 DEK preferentially binds supercoiled and four-way junction (cruciform) DNA but not in a sequence-specific manner; in the presence of topoisomerase II, DEK stimulates intermolecular catenation of circular DNA; DEK also increases the probability of intermolecular ligation by DNA ligase. Filter binding assays, band-shift assays, in vitro catenation and ligation assays Nucleic acids research High 14627833
2005 The SAF-box peptide (aa 137–187) alone binds DNA weakly, but the larger fragment (aa 87–187) binds efficiently and introduces negative supercoils (in contrast to full-length DEK which introduces positive supercoils). Flanking regions aa 68–87 and 187–250 are required for positive supercoil formation. In vitro DNA-binding assays, supercoiling assay with truncation mutants Nucleic acids research High 15722484
2007 DEK and PARP1 restrict chromatin access and repress transcription; the histone chaperone SET displaces DEK and PARP1 from chromatin to permit RNA Pol II transcription. When NAD+ is present, PARP1 poly(ADP-ribosyl)ates DEK and evicts it (and itself) from chromatin, allowing Mediator loading and transcription independent of SET. An artificial DEK variant resistant to SET and PARP1 represses transcription, demonstrating DEK removal is required. In vitro chromatin transcription reconstitution, nuclease accessibility assay, Mediator recruitment assay, dominant-negative DEK variant Nature structural & molecular biology High 17529993
2008 During apoptosis, DEK is extensively modified by poly(ADP-ribosyl)ation (PARylation) and phosphorylation. These modifications are accompanied by DEK removal from chromatin and its release into the extracellular space. DEK promotes DNA repair and protects cells from genotoxic agents that trigger PARP activation. Released, modified DEK is recognized by autoantibodies from juvenile idiopathic arthritis patients. In vivo modification analysis, DEK knockdown/interference experiments, cell viability/DNA damage assays, autoantibody binding assays Molecular and cellular biology High 18332104
2005 DEK undergoes acetylation in vivo at lysine residues within the N-terminal 70 amino acids. Acetylation decreases DEK's affinity for DNA promoter elements (consistent with transcriptional repression). PCAF/P300 acetylase overexpression or deacetylase inhibition relocates DEK to interchromatin granule clusters (IGCs), sub-nuclear RNA processing structures; a synthetic PCAF inhibitor blocks this movement. In vivo acetylation assay, DNA binding assay, immunofluorescence, pharmacologic inhibition, PCAF overexpression The Journal of biological chemistry High 15987677
2006 DEK interacts with histones and inhibits p300- and PCAF-mediated histone acetyltransferase (HAT) activity; ChIP assays show DEK recruitment to a target promoter correlates with histone H3 and H4 hypoacetylation of chromatin. Co-immunoprecipitation, in vitro HAT inhibition assay, chromatin immunoprecipitation (ChIP) FEBS letters Medium 16696975
2006 DEK is actively secreted by macrophages in both free form and in exosomes; secretion is stimulated by IL-8 and modulated by casein kinase 2, and is inhibited by dexamethasone and cyclosporine A. Extracellular DEK functions as a chemotactic factor attracting neutrophils, CD8+ T lymphocytes, and NK cells. ELISA, exosome isolation and characterization, chemotaxis assay, pharmacologic modulation Molecular and cellular biology High 17030615
2011 DEK directly interacts with Heterochromatin Protein 1α (HP1α) and markedly enhances HP1α binding to trimethylated H3K9 (H3K9me3). Loss of Dek in Drosophila leads to a Suppressor of Variegation [Su(var)] phenotype and global reduction in heterochromatin, establishing DEK as essential for heterochromatin integrity. Direct protein interaction assay, genetic Drosophila Su(var) screen, immunofluorescence of heterochromatin markers, DEK knockout analysis Genes & development High 21460035
2011 DEK depletion in human cancer cell lines and primary Dek knockout MEFs induces a DNA damage response (γH2AX, FANCD2), with ATM pathway activation and DNA-PK pathway suppression. Dek knockout MEFs show defects specifically in non-homologous end joining (NHEJ) repair. DEK knockdown in cell lines and xenografts, Dek KO MEFs, γH2AX/FANCD2 immunostaining, NHEJ reporter assay, kinase pathway analysis Nucleic acids research High 21653549
2011 FBXW7 (SCF E3 ubiquitin ligase component) targets DEK for ubiquitin-mediated degradation; loss of FBXW7 in mouse intestine leads to DEK accumulation and altered RNA splicing of tropomyosin (TPM), promoting cell division. DEK accumulation and altered TPM splicing were also detected in FBXW7 mutant human colorectal tumor tissues. Conditional Fbxw7 knockout mouse model, immunohistochemistry, RNA splicing analysis, human tumor tissue analysis The Journal of experimental medicine Medium 21282377
2013 Exogenous DEK can penetrate cells, translocate to the nucleus, and perform endogenous nuclear functions. Adjacent cells take up DEK secreted from synovial macrophages. DEK internalization is heparan sulfate-dependent. Cellular uptake of DEK into DEK knockdown cells corrects global heterochromatin depletion and DNA repair deficits. Live cell imaging, heparan sulfate inhibitor experiments, DEK knockdown rescue assay, heterochromatin marker immunostaining Proceedings of the National Academy of Sciences of the United States of America High 23569252
2014 DEK regulates the differential HIRA- and DAXX/ATRX-dependent distribution of histone variant H3.3 on chromosomes. DEK loss causes non-nucleosomal H3.3 re-routing from PML nuclear bodies to chromatin, HIRA-dependent widespread H3.3 deposition, displacement of PML bodies and ATRX from telomeres, redistribution of H3.3 from telomeres, and induction of a fragile telomere phenotype. Live cell imaging, ChIP, immunofluorescence, DEK depletion in somatic and ES cells, telomere FISH Genome research High 25049225
2012 DEK is identified as a binding partner of the transcription factor C/EBPα on chromatin; this association is disrupted by phosphorylation of C/EBPα at serine 21. DEK is specifically recruited with C/EBPα to the GCSFR3 promoter to enhance its activation. Genetic depletion of DEK reduces C/EBPα-driven expression of granulocytic target genes and disrupts G-CSF-mediated granulocytic differentiation of human CD34+ BM cells. Immuno-affinity purification combined with quantitative mass spectrometry, ChIP, DEK genetic depletion, myeloid differentiation assay Blood High 22474248
2014 DEK promotes cellular proliferation under DNA replication stress conditions by facilitating replication fork progression. DEK also protects from transmission of DNA damage to daughter cell generations, resolving problematic DNA/chromatin structures at the replication fork. DEK depletion, DNA fiber assay (fork progression), DNA damage transmission assay Oncogene Medium 25347734
2017 DEK is required for homologous recombination (HR) repair of DNA double-strand breaks. DEK-deficient cells show impaired γH2AX phosphorylation and attenuated RAD51 filament formation. DEK forms a complex with RAD51 (but not BRCA1). Loss of NHEJ in DEK knockout cells is insufficient to impair immunoglobulin class switching, but DEK knockout cells are synthetic lethal with NHEJ inhibition. HR reporter assay (episomal and integrated), RAD51 foci immunostaining, co-immunoprecipitation (DEK-RAD51), Ig class switch recombination assay in KO mice, NHEJ inhibitor sensitivity Scientific reports High 28317934
2019 Extracellular DEK enhances hematopoietic stem cell (HSC) expansion and regulates HSC and HPC numbers through CXCR2 and heparan sulfate proteoglycans (HSPGs), activating ERK1/2, AKT, and p38 MAPK signaling. DEK mutants lacking nuclear translocation signal or DNA-binding ability still altered HSC/HPC numbers, indicating the nuclear function of DEK is not required for its extracellular hematopoietic cytokine activity. Recombinant DEK treatment of human/mouse HSCs, flow cytometry phenotyping, transplantation assay, Cxcr2-/- mice, CXCR2 blocking antibodies, HSPG inhibitors, phosphorylation analysis, DEK domain mutants The Journal of clinical investigation High 31107242
2021 Nuclear DEK maintains HSC quiescence and self-renewal by recruiting the corepressor NCoR1 to repress H3K27 acetylation and restrict chromatin accessibility, governing expression of quiescence-associated genes (Akt1/2, Ccnb2, p21). DEK deficiency reduces quiescence and activates mTOR signaling; mTOR inhibition restores maintenance of Dek-KO HSCs. Conditional DEK KO in mice, ATAC-seq, ChIP-seq for H3K27ac, co-immunoprecipitation (DEK-NCoR1), mTOR inhibitor rescue experiment, transplantation assay The Journal of experimental medicine High 33755722
2020 Phosphorylated DEK protein modulates intron retention (IR) during muscle satellite cell quiescence exit. Dek overexpression in vivo results in global decrease of IR, premature differentiation of quiescent satellite cells, and undermined muscle regeneration. RNA-seq analysis of satellite cells, Dek overexpression in vivo, muscle regeneration assay Developmental cell Medium 32502396
2009 Long-term DEK knockdown in melanoma cells causes premature senescence; short-term DEK depletion attenuates resistance to DNA-damaging agents. DEK transcriptionally activates the antiapoptotic gene MCL-1 (with no effect on p53, BCL-2, or BCL-xL), establishing a selective DEK-MCL-1 pathway in melanoma chemoresistance. shRNA knockdown, senescence assays, DNA damage sensitivity assays, Western blot for apoptotic machinery Cancer research Medium 19679545
2006 The DEK promoter contains functional E2F binding sites; endogenous E2F binds the DEK promoter in vivo (ChIP), and E2F transactivates DEK expression. Mutation of E2F binding sites eliminates this transactivation. Chromatin immunoprecipitation (ChIP), promoter-reporter assay with E2F binding site mutations Cell cycle (Georgetown, Tex.) Medium 16721057
2002 The DEK promoter contains a functional inverted CCAAT box and a YY1 consensus binding site; point mutations in these sites markedly diminish transcriptional activity. NF-Y binds the CCAAT box and YY1 binds its consensus site in the dek promoter. Promoter-reporter assay with site-directed mutagenesis, transcription factor binding assays, electrophoretic mobility shift assay (EMSA) Oncogene Medium 12483538
2003 Recombinant DEK binds specifically to class II MHC Y-box sequences (DQA1*0101 and DQA1*0501, but not consensus DRA Y box) in a gene- and allele-specific manner. DEK participates with NF-Y in the DQA1 Y-box binding complex (demonstrated by supershift assays). DNase I footprinting identified crucial DEK-binding residues. EMSA, supershift assay with anti-DEK antibodies, recombinant protein binding assay, DNase I footprinting, dissociation constant measurement Arthritis research & therapy Medium 12823858
2011 DEK autoantibodies (IgG2 isotype) in JIA synovial fluid primarily recognize the C-terminal portion of DEK protein and exhibit higher affinity for acetylated DEK. DEK undergoes acetylation on an unprecedented number of lysine residues in the inflamed joint, as demonstrated by nano-LC-MS/MS. Affinity-column chromatography, 2D gel electrophoresis, nano-LC-MS/MS, ELISA, immunoprecipitation Arthritis and rheumatism Medium 21280010
2014 DEK overexpression in Ron receptor-positive breast cancer stimulates production and secretion of Wnt ligands to sustain an autocrine/paracrine canonical β-catenin signaling loop, promoting tumor cell growth and invasion. Dek is a downstream target of Ron receptor activation. Dek KO in MMTV-Ron mouse model, Dek complementation of cell lines, Wnt ligand secretion assay, β-catenin signaling assay, invasion assay Oncogene Medium 24954505
2016 DEK directly binds to a DEK-responsive element (DRE) in the VEGF promoter and indirectly binds to the hypoxia response element (HRE) through interaction with HIF-1α, recruiting HIF-1α and p300 to the VEGF promoter, thereby promoting VEGF transcription and tumor angiogenesis. ChIP assay, luciferase reporter assay, co-immunoprecipitation (DEK-HIF-1α), in vitro angiogenesis assay, in vivo xenograft Oncotarget Medium 26988756
2014 DEK loss in HNSCC cells reduces expression of the oncogenic p53 family member ΔNp63; exogenous ΔNp63 expression rescues proliferative defects caused by DEK loss, establishing a functional DEK-ΔNp63 oncogenic pathway that promotes HNSCC growth. DEK knockdown, Western blot, ΔNp63 rescue experiment, Dek KO transgenic mouse model of HPV16 E7-induced HNSCC Oncogene Medium 24608431
2013 Expression of DEK-NUP214 fusion protein in myeloid cell lines increases cellular proliferation by upregulating mTOR (specifically mTORC1), leading to increased protein synthesis and a metabolic shift toward oxidative phosphorylation. mTORC1 inhibitor everolimus selectively reverses DEK-NUP214-induced proliferation. DEK-NUP214 expression in U937/PL-21 cells, Western blot (mTOR, p70 S6K, Akt), global translation assay, metabolic assay, mTOR inhibitor treatment BMC cancer Medium 24073922
2013 DEK depletion in NSCLC cells inhibits cellular migration by reducing RhoA expression and RhoA-GTP (active) levels, with concomitant reduction of downstream phosphorylated MLC2, placing DEK upstream of the RhoA/ROCK/MLC signaling pathway in lung cancer cell migration. DEK knockdown, RhoA activity assay (GTP pulldown), Western blot for pathway components, migration assay The journal of histochemistry and cytochemistry Low 23571382
2015 DEK overexpression causes its aberrant retention on mitotic chromosomes (normally DEK dissociates from DNA in early prophase and re-associates during telophase), co-localizes with anaphase bridges and micronuclei, and is sufficient to stimulate micronucleus formation, promoting chromosomal instability. Immunofluorescence during mitosis, DEK overexpression in keratinocytes and cancer cells, micronucleus assay Cell cycle (Georgetown, Tex.) Medium 25945971
2022 METTL3 promotes stability of DEK mRNA through m6A modification at the DEK 3'UTR, increasing DEK mRNA half-life. METTL3 enriches DEK mRNA (RIP assay) and MeRIP confirms m6A modification. DEK knockdown reverses METTL3-driven gastric cancer cell proliferation and migration in vitro and in vivo. RIP assay, MeRIP assay, mRNA half-life assay, dot blot for m6A, rescue knockdown experiment, in vivo lung metastasis model International journal of molecular sciences Medium 35742899
2011 DEK positively regulates the engrafting capability of long-term repopulating hematopoietic stem cells (HSCs), while DEK knockout mice have significantly enhanced hematopoietic progenitor cell (HPC) colony formation. Purified recombinant DEK protein directly inhibits colony formation by CFU-GM, BFU-E, and CFU-GEMM in a dose-dependent manner. Dek KO mice, recombinant protein treatment of HSC/HPC, colony formation assay, single-cell proliferation assay, competitive transplantation Stem cells and development High 21943234
2023 PG545 inhibits endocytosis of DEK (a heparan-sulfate proteoglycan interacting protein), sequestering DEK in the tumor microenvironment and reducing nuclear DEK needed for homologous recombination repair (HRR), thereby sensitizing ovarian cancer cells to PARP inhibitors. DEK endocytosis assay, HRR reporter assay, RAD51 immunostaining, PARP inhibitor synergy assay in vitro and in vivo Oncogene Medium 37550562

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 FBXW7 influences murine intestinal homeostasis and cancer, targeting Notch, Jun, and DEK for degradation. The Journal of experimental medicine 157 21282377
2009 Melanoma proliferation and chemoresistance controlled by the DEK oncogene. Cancer research 119 19679545
2004 The DEK protein--an abundant and ubiquitous constituent of mammalian chromatin. Gene 102 15563827
2006 DEK Expression is controlled by E2F and deregulated in diverse tumor types. Cell cycle (Georgetown, Tex.) 98 16721057
2005 Gains and overexpression identify DEK and E2F3 as targets of chromosome 6p gains in retinoblastoma. Oncogene 94 16007192
2004 Phosphorylation by protein kinase CK2 changes the DNA binding properties of the human chromatin protein DEK. Molecular and cellular biology 89 15199154
2008 DEK is a poly(ADP-ribose) acceptor in apoptosis and mediates resistance to genotoxic stress. Molecular and cellular biology 87 18332104
2002 The ubiquitous chromatin protein DEK alters the structure of DNA by introducing positive supercoils. The Journal of biological chemistry 87 11997399
2017 DEK-targeting DNA aptamers as therapeutics for inflammatory arthritis. Nature communications 86 28165452
2007 SET and PARP1 remove DEK from chromatin to permit access by the transcription machinery. Nature structural & molecular biology 86 17529993
2001 Subcellular localization of the human proto-oncogene protein DEK. The Journal of biological chemistry 86 11333257
2020 Dek Modulates Global Intron Retention during Muscle Stem Cells Quiescence Exit. Developmental cell 82 32502396
2006 The DEK nuclear autoantigen is a secreted chemotactic factor. Molecular and cellular biology 82 17030615
2009 Overexpression of the cellular DEK protein promotes epithelial transformation in vitro and in vivo. Cancer research 81 19223548
2011 The DEK oncoprotein is a Su(var) that is essential to heterochromatin integrity. Genes & development 80 21460035
2011 The human DEK oncogene regulates DNA damage response signaling and repair. Nucleic acids research 78 21653549
2021 DEK-AFF2 Carcinoma of the Sinonasal Region and Skull Base: Detailed Clinicopathologic Characterization of a Distinctive Entity. The American journal of surgical pathology 75 34049316
2010 Control of tumorigenesis and chemoresistance by the DEK oncogene. Clinical cancer research : an official journal of the American Association for Cancer Research 74 20501624
2004 Functional domains of the ubiquitous chromatin protein DEK. Molecular and cellular biology 73 15199153
2003 Structure-specific binding of the proto-oncogene protein DEK to DNA. Nucleic acids research 72 14627833
2014 t(6;9)(p22;q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients. Haematologica 65 24441146
2011 DEK in the synovium of patients with juvenile idiopathic arthritis: characterization of DEK antibodies and posttranslational modification of the DEK autoantigen. Arthritis and rheumatism 63 21280010
2012 Stacking the DEK: from chromatin topology to cancer stem cells. Cell cycle (Georgetown, Tex.) 61 23255114
2014 The DEK oncogene promotes cellular proliferation through paracrine Wnt signaling in Ron receptor-positive breast cancers. Oncogene 58 24954505
2014 The PML-associated protein DEK regulates the balance of H3.3 loading on chromatin and is important for telomere integrity. Genome research 58 25049225
2021 DEK-AFF2 fusion-associated papillary squamous cell carcinoma of the sinonasal tract: clinicopathologic characterization of seven cases with deceptively bland morphology. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 57 34108636
2003 Aberrant expression of HOXA9, DEK, CBL and CSF1R in acute myeloid leukemia. Leukemia & lymphoma 55 14738146
2020 DEK-targeting aptamer DTA-64 attenuates bronchial EMT-mediated airway remodelling by suppressing TGF-β1/Smad, MAPK and PI3K signalling pathway in asthma. Journal of cellular and molecular medicine 54 33124760
2005 p300/CBP-associated factor drives DEK into interchromatin granule clusters. The Journal of biological chemistry 54 15987677
2020 Novel DEK-Targeting Aptamer Delivered by a Hydrogel Microneedle Attenuates Collagen-Induced Arthritis. Molecular pharmaceutics 53 33253580
2010 DEK oncoprotein regulates transcriptional modifiers and sustains tumor initiation activity in high-grade neuroendocrine carcinoma of the lung. Oncogene 53 20543864
2006 Regulation of histone acetyltransferase activity of p300 and PCAF by proto-oncogene protein DEK. FEBS letters 51 16696975
2015 Identification of DEK as a potential therapeutic target for neuroendocrine prostate cancer. Oncotarget 49 25544761
1992 Translocation t(6;9) in acute non-lymphocytic leukaemia results in the formation of a DEK-CAN fusion gene. Bailliere's clinical haematology 49 1308167
2012 C/EBPα and DEK coordinately regulate myeloid differentiation. Blood 45 22474248
1999 Isolation and characterization of Dek, a Drosophila eph receptor protein tyrosine kinase. Molecular and cellular neurosciences 45 10356296
2014 DEK promotes HPV-positive and -negative head and neck cancer cell proliferation. Oncogene 43 24608431
2008 DEK overexpression in uterine cervical cancers. Pathology international 43 18477217
2005 The SAF-box domain of chromatin protein DEK. Nucleic acids research 43 15722484
2002 YY1 and NF-Y binding sites regulate the transcriptional activity of the dek and dek-can promoter. Oncogene 43 12483538
2013 Intercellular trafficking of the nuclear oncoprotein DEK. Proceedings of the National Academy of Sciences of the United States of America 41 23569252
2011 Oncoprotein DEK as a tissue and urinary biomarker for bladder cancer. BMC cancer 41 21663673
2020 CD36 upregulates DEK transcription and promotes cell migration and invasion via GSK-3β/β-catenin-mediated epithelial-to-mesenchymal transition in gastric cancer. Aging 40 33232276
2017 DEK promoted EMT and angiogenesis through regulating PI3K/AKT/mTOR pathway in triple-negative breast cancer. Oncotarget 40 29228721
2015 IRAK1 is a novel DEK transcriptional target and is essential for head and neck cancer cell survival. Oncotarget 39 26527316
2012 DEK overexpression is correlated with the clinical features of breast cancer. Pathology international 39 22360505
2015 The DEK oncoprotein and its emerging roles in gene regulation. Leukemia 38 25765544
2012 The DEK oncogene is a target of steroid hormone receptor signaling in breast cancer. PloS one 38 23071688
2022 Nuclear expression of AFF2 C-terminus is a sensitive and specific ancillary marker for DEK::AFF2 carcinoma of the sinonasal tract. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 37 35701667
2020 Middle Ear and Temporal Bone Nonkeratinizing Squamous Cell Carcinomas With DEK-AFF2 Fusion: An Emerging Entity. The American journal of surgical pathology 37 32366754
2015 Dissecting the Potential Interplay of DEK Functions in Inflammation and Cancer. Journal of oncology 37 26425120
2013 Forced expression of the DEK-NUP214 fusion protein promotes proliferation dependent on upregulation of mTOR. BMC cancer 36 24073922
1992 Dek-can rearrangement in translocation (6;9)(p23;q34). Leukemia 35 1602786
2017 DEK is required for homologous recombination repair of DNA breaks. Scientific reports 34 28317934
2021 Nuclear DEK preserves hematopoietic stem cells potential via NCoR1/HDAC3-Akt1/2-mTOR axis. The Journal of experimental medicine 33 33755722
2019 Secreted nuclear protein DEK regulates hematopoiesis through CXCR2 signaling. The Journal of clinical investigation 33 31107242
2014 The human oncoprotein and chromatin architectural factor DEK counteracts DNA replication stress. Oncogene 33 25347734
2011 DEK regulates hematopoietic stem engraftment and progenitor cell proliferation. Stem cells and development 32 21943234
2012 Silencing of the DEK gene induces apoptosis and senescence in CaSki cervical carcinoma cells via the up-regulation of NF-κB p65. Bioscience reports 30 22390170
2013 Concise review: role of DEK in stem/progenitor cell biology. Stem cells (Dayton, Ohio) 29 23733396
2017 Promotion of cell proliferation by the proto-oncogene DEK enhances oral squamous cell carcinogenesis through field cancerization. Cancer medicine 28 28834425
2022 The m6A Methyltransferase METTL3-Mediated N6-Methyladenosine Modification of DEK mRNA to Promote Gastric Cancer Cell Growth and Metastasis. International journal of molecular sciences 27 35742899
2016 The DEK oncogene activates VEGF expression and promotes tumor angiogenesis and growth in HIF-1α-dependent and -independent manners. Oncotarget 27 26988756
2011 DEK expression in melanocytic lesions. Human pathology 26 21316078
2022 First Report of Thoracic Carcinoma With DEK::AFF2 Rearrangement: A Case Report. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 24 35773081
2014 Mechanisms underlying cancer growth and apoptosis by DEK overexpression in colorectal cancer. PloS one 24 25340858
2018 MicroRNA-1292-5p inhibits cell growth, migration and invasion of gastric carcinoma by targeting DEK. American journal of cancer research 23 30094096
2017 Overexpression of the human DEK oncogene reprograms cellular metabolism and promotes glycolysis. PloS one 23 28558019
2016 Critical role of DEK and its regulation in tumorigenesis and metastasis of hepatocellular carcinoma. Oncotarget 23 27057626
2010 The oncogene DEK promotes leukemic cell survival and is downregulated by both Nutlin-3 and chlorambucil in B-chronic lymphocytic leukemic cells. Clinical cancer research : an official journal of the American Association for Cancer Research 23 20215548
2022 DEK::AFF2 Fusion Carcinomas of Head and Neck. Advances in anatomic pathology 22 36221219
2017 Silencing DEK downregulates cervical cancer tumorigenesis and metastasis via the DEK/p-Ser9-GSK-3β/p-Tyr216-GSK-3β/β-catenin axis. Oncology reports 22 28627610
2020 Cordycepin Inhibits Cancer Cell Proliferation and Angiogenesis through a DEK Interaction via ERK Signaling in Cholangiocarcinoma. The Journal of pharmacology and experimental therapeutics 21 32102917
2018 Dek overexpression in murine epithelia increases overt esophageal squamous cell carcinoma incidence. PLoS genetics 21 29538372
2015 DEK over-expression promotes mitotic defects and micronucleus formation. Cell cycle (Georgetown, Tex.) 21 25945971
2022 Long Non-Coding LEF1-AS1 Sponge miR-5100 Regulates Apoptosis and Autophagy in Gastric Cancer Cells via the miR-5100/DEK/AMPK-mTOR Axis. International journal of molecular sciences 20 35563178
2020 MicroRNA-138 promotes neuroblastoma SH-SY5Y cell apoptosis by directly targeting DEK in Alzheimer's disease cell model. BMC neuroscience 19 32736520
2017 DEK oncogene is overexpressed during melanoma progression. Pigment cell & melanoma research 19 27893188
2017 DEK proto-oncogene is highly expressed in astrocytic tumors and regulates glioblastoma cell proliferation and apoptosis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 19 28670979
2018 The DEK Oncoprotein Functions in Ovarian Cancer Growth and Survival. Neoplasia (New York, N.Y.) 18 30412857
2013 DEK depletion negatively regulates Rho/ROCK/MLC pathway in non-small cell lung cancer. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 18 23571382
2003 DEK binding to class II MHC Y-box sequences is gene- and allele-specific. Arthritis research & therapy 18 12823858
2021 Circular RNA circ_0000039 enhances gastric cancer progression through miR-1292-5p/DEK axis. Cancer biomarkers : section A of Disease markers 17 33104023
2005 Distribution of the chromatin protein DEK distinguishes active and inactive CD21/CR2 gene in pre- and mature B lymphocytes. International immunology 17 15908448
2015 MicroRNA-592 targets DEK oncogene and suppresses cell growth in the hepatocellular carcinoma cell line HepG2. International journal of clinical and experimental pathology 16 26722432
2022 miR-181-5p attenuates neutrophilic inflammation in asthma by targeting DEK. International immunopharmacology 15 36115279
2017 Loss of DEK induces radioresistance of murine restricted hematopoietic progenitors. Experimental hematology 14 29288703
2015 SiRNA knockdown of the DEK nuclear protein mRNA enhances apoptosis and chemosensitivity of canine transitional cell carcinoma cells. Veterinary journal (London, England : 1997) 14 25773167
2022 Exosomal DEK removes chemoradiotherapy resistance by triggering quiescence exit of breast cancer stem cells. Oncogene 13 35351996
2023 Sinonasal Adenosquamous Carcinoma - Morphology and Genetic Drivers Including Low- and High-Risk Human Papillomavirus mRNA, DEK::AFF2 Fusion, and MAML2 Rearrangement. Head and neck pathology 12 36849671
2020 DEK Expression in Breast Cancer Cells Leads to the Alternative Activation of Tumor Associated Macrophages. Cancers 12 32708944
2017 A role for intracellular and extracellular DEK in regulating hematopoiesis. Current opinion in hematology 12 28306668
2003 Minireview: DEK and gene regulation, oncogenesis and AIDS. Anticancer research 12 12894590
2024 Sinonasal Squamous Cell Carcinoma with DEK::AFF2 Rearrangement : An Aggressive Cancer with Bland Morphology. The American journal of surgical pathology 11 39132684
2023 PG545 sensitizes ovarian cancer cells to PARP inhibitors through modulation of RAD51-DEK interaction. Oncogene 11 37550562
2021 Sevoflurane Limits Glioma Progression by Regulating Cell Proliferation, Apoptosis, Migration, and Invasion via miR-218-5p/DEK/β-Catenin Axis in Glioma. Cancer management and research 11 33664593
2018 The Complexity of DEK Signaling in Cancer Progression. Current cancer drug targets 11 28530531
2018 Sex differences in DEK expression in the anterior cingulate cortex and its association with dementia severity in schizophrenia. Schizophrenia research 11 30017458
2024 DEK :: AFF2 Fusion Sinonasal and Skull Base Nonkeratinizing Squamous Cell Carcinoma : A Clinical Outcome Study Compared With Conventional Sinonasal Squamous Cell Carcinoma. The American journal of surgical pathology 10 39719672
2020 Loss of DEK Expression Induces Alzheimer's Disease Phenotypes in Differentiated SH-SY5Y Cells. Frontiers in molecular neuroscience 10 33304240

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