Affinage

TFDP1

Transcription factor Dp-1 · UniProt Q14186

Length
410 aa
Mass
45.1 kDa
Annotated
2026-04-28
100 papers in source corpus 37 papers cited in narrative 37 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TFDP1 encodes the transcription factor DP-1, an obligate heterodimerization partner of E2F-family proteins that together form the sequence-specific DNA-binding E2F/DP complex governing S-phase gene expression and cell cycle progression (PMID:8405995, PMID:8446173, PMID:8223441). Heterodimerization occurs through the hydrophobic heptad repeat and marked box domains; the resulting complex activates transcription of cyclins A and E, CDK2, and DHFR, and is negatively regulated by pRb (which contacts both E2F1 and DP-1 marked box domains), cyclin A/CDK2-mediated phosphorylation that inhibits DNA binding, ARF (which directly binds free DP-1 to disrupt E2F1/DP-1 heterodimerization independently of p53), and Kbtbd5-mediated ubiquitination and degradation of DP-1 (PMID:16360038, PMID:7969176, PMID:16135794, PMID:25940086). Nuclear import of the E2F1/TFDP1 complex requires KPNA2, and unpartnered DP-1 is retained in the cytoplasm and targeted for ubiquitin-dependent degradation (PMID:31783876, PMID:9989809). Beyond canonical cell cycle gene regulation, TFDP1 modulates global chromatin accessibility through transcriptional control of canonical histones (PMID:38361031).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1993 High

    Identification of DP-1 as an obligate heterodimeric partner of E2F-1 resolved the long-standing question of how high-affinity, sequence-specific E2F DNA binding and transcriptional activation are achieved, and established that the resulting heterodimer is a target of pRb-mediated repression.

    Evidence Co-immunoprecipitation, EMSA, and transcriptional reporter assays in mammalian, yeast, and Drosophila cells

    PMID:8223441 PMID:8405995 PMID:8446173

    Open questions at the time
    • Stoichiometry and affinity of the heterodimer not quantified
    • Whether DP-1 contributes transactivation function independently of E2F was unclear
    • In vivo physiological requirement not yet tested
  2. 1994 High

    Mapping the hydrophobic heptad repeat domain (DP-1 aa 196–245) as the heterodimerization interface and demonstrating cell-cycle-dependent DP-1 phosphorylation and cyclin A/CDK2-mediated inhibition of DNA binding defined the structural and regulatory logic governing E2F/DP activity.

    Evidence Yeast two-hybrid, domain deletion mapping, in vitro kinase assays with purified components, phosphopeptide analysis

    PMID:7969176 PMID:8039504 PMID:8207796

    Open questions at the time
    • Precise phosphorylation sites on DP-1 responsible for DNA-binding inhibition not mapped
    • Whether cyclin A/CDK2 phosphorylates DP-1 directly or only E2F-1 in the heterodimer was unresolved
  3. 1995 High

    Discovery that MDM2 stimulates and p53 inhibits E2F1/DP-1 transcriptional activity, and that E2F-1/DP-1 overexpression induces p53 and apoptosis, placed the E2F/DP complex at the intersection of proliferation and apoptosis pathways.

    Evidence Co-immunoprecipitation, GST pulldown, transcriptional assays, inducible expression with flow cytometry and apoptosis measurement

    PMID:7791903 PMID:8524253 PMID:8557038

    Open questions at the time
    • Physiological relevance of MDM2 co-activation versus p53 repression not resolved in normal cells
    • Whether DP-1 directly contacts MDM2 or p53 independently of E2F-1 needed clarification
  4. 1996 High

    Demonstration that dominant-negative DP-1 mutants retaining E2F binding but lacking DNA-binding activity arrest cells in G1, and that p53 directly competes with E2F-1 for DP-1 binding, established DP-1 as a rate-limiting factor for E2F-dependent S-phase entry.

    Evidence Dominant-negative transfection with flow cytometry, rescue experiments, domain mutagenesis, and EMSA competition assays

    PMID:8668186 PMID:8816502

    Open questions at the time
    • Whether p53-DP-1 complex has a function beyond sequestration was unknown
    • In vivo relevance of p53-DP-1 competition not tested genetically
  5. 1999 High

    Showing that E2F-1 binding rescues DP-1 from cytoplasmic polyubiquitination and promotes its nuclear entry revealed that subcellular partitioning and protein stability are coupled to heterodimerization status.

    Evidence Immunolocalization, cell fractionation, immunoprecipitation of ubiquitinated species, inducible expression

    PMID:9989809

    Open questions at the time
    • The E3 ubiquitin ligase responsible for DP-1 cytoplasmic degradation was not identified
    • Whether regulated deubiquitination plays a role was unknown
  6. 2003 High

    Dp1 knockout in mice causing embryonic lethality due to failed trophoblast expansion and endoreduplication — not rescued by p53 loss — demonstrated an essential, p53-independent developmental role for DP-1 in extra-embryonic tissues.

    Evidence Dp1 knockout mouse, histological analysis, p53 genetic rescue cross

    PMID:12588846

    Open questions at the time
    • Which E2F partner(s) mediate the extra-embryonic requirement was not determined
    • Molecular targets of E2F/DP in endoreduplication not identified
    • Why embryonic tissues tolerate Dp1 loss (later shown via chimera analysis) needed explanation
  7. 2004 High

    Chimeric mouse analysis showing that Dp1-null ES cells contribute normally to most embryonic tissues, without compensatory DP-2 upregulation, revealed that DP-1 is largely dispensable for embryonic somatic cell proliferation, restricting its essential role to extra-embryonic lineages.

    Evidence Dp1-null ES cell chimeras, X-Gal staining, Western blot, expression profiling

    PMID:15282318

    Open questions at the time
    • Whether DP-2 functionally compensates despite unchanged protein levels was not formally tested
    • Adult tissue-specific requirements not examined
  8. 2005 High

    The crystal structure of the RbC–E2F1–DP1 complex revealed that the marked box domains of both E2F1 and DP1 directly contact the Rb C-terminal domain, and phosphorylation at specific Rb sites destabilizes these contacts, providing an atomic-level mechanism for CDK-driven E2F/DP release.

    Evidence X-ray crystallography with phosphorylation-site mutagenesis and biochemical binding assays

    PMID:16360038

    Open questions at the time
    • Structure of full-length DP-1 or of DP-1 with other E2F family members not determined
    • Dynamics of the release in vivo not captured
  9. 2005 High

    Direct binding of ARF to DP-1 that disrupts E2F1/DP-1 heterodimerization independently of p53/Mdm2, and identification of dominant-negative DP-1 isoforms (DP-1α), defined two distinct mechanisms that restrain E2F/DP activity by targeting DP-1 availability.

    Evidence GST pulldown, ChIP at dhfr promoter, cell cycle analysis in p53-null cells; yeast two-hybrid and immunofluorescence for isoform characterization

    PMID:15863509 PMID:16135794

    Open questions at the time
    • Physiological abundance and tissue distribution of DP-1α isoform unknown
    • Whether ARF-DP-1 binding occurs at specific genomic loci genome-wide not tested
  10. 2015 High

    Identification of Kbtbd5 as a direct E3 ligase adapter that ubiquitinates DP-1 via its dimerization domain, with genetic epistasis showing that Kbtbd5-null lethality is rescued by E2F1 loss, established a tissue-specific ubiquitin-dependent mechanism controlling E2F/DP activity in skeletal muscle.

    Evidence Yeast two-hybrid, GST pulldown, ubiquitination assay, Kbtbd5 knockout mouse, E2F1-null genetic rescue

    PMID:25940086

    Open questions at the time
    • Whether Kbtbd5 acts as the Cullin adapter or a direct RING E3 was not fully clarified
    • Other tissues regulated by Kbtbd5-DP-1 axis not explored
  11. 2019 High

    Demonstration that KPNA2 mediates nuclear import of the E2F1/TFDP1 complex, with KPNA2 depletion causing cytoplasmic retention and loss of target gene (STMN1) expression, defined the nuclear transport pathway for E2F/DP.

    Evidence siRNA knockdown, subcellular fractionation, co-immunoprecipitation, ChIP, LC-MS/MS proteomics in HCC cells

    PMID:31783876

    Open questions at the time
    • Whether KPNA2 recognizes a classical NLS on E2F1, DP-1, or both was not mapped
    • Redundancy with other karyopherin-α isoforms not tested
  12. 2023 High

    Showing that deregulated E2F1 transcriptionally induces TFDP1 itself via GC-rich promoter elements, while DP-1 knockdown derepresses ARF, revealed a positive-feedback/failsafe circuit in which excessive E2F activity amplifies DP-1 but simultaneously triggers ARF-mediated restraint.

    Evidence E2F1 overexpression, adenovirus E1a, ChIP on TFDP1 promoter, shRNA knockdown, qRT-PCR in fibroblasts

    PMID:37141667

    Open questions at the time
    • Whether this feedback circuit operates in all cell types or is context-specific was not determined
    • Quantitative thresholds for feedback engagement not defined
  13. 2024 High

    A genome-wide CRISPR/ATAC-see screen identified TFDP1 as a regulator of global chromatin accessibility beyond classical E2F target genes, acting through transcriptional control of canonical histone expression, expanding TFDP1's role from cell cycle gene regulation to a broader chromatin organizer.

    Evidence Genome-wide CRISPR screen, ATAC-see, ATAC-seq, TFDP1 knockout with expression analysis

    PMID:38361031

    Open questions at the time
    • Which E2F partner(s) cooperate with DP-1 for histone gene regulation not identified
    • Whether reduced chromatin accessibility is a direct or indirect consequence of histone loss not fully resolved
    • Impact on heterochromatin versus euchromatin domains not dissected

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full-length structure of DP-1 in complex with different E2F family members, the complete repertoire of E3 ligases targeting DP-1 across tissues, the genome-wide interplay between ARF-DP-1 and Rb-E2F/DP regulatory arms, and whether DP-1's chromatin accessibility function via histone regulation is separable from its canonical role in activating S-phase genes.
  • No full-length DP-1 structure available
  • Tissue-specific E3 ligase landscape for DP-1 degradation uncharacterized
  • Genome-wide ARF-DP-1 binding sites not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 5
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 3 GO:0005829 cytosol 3
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1640170 Cell Cycle 5 R-HSA-5357801 Programmed Cell Death 2 R-HSA-4839726 Chromatin organization 1
Partners
CDKN2AE2F1KBTBD5KPNA2MDM2RB1SOCS3TP53
Complex memberships
E2F/DP heterodimerE2F/DP/Rb complexE2F/DP/p107 complex

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 Human DP-1 (TFDP1) heterodimerizes with E2F-1 both in vivo and in vitro, and this heterodimer leads to enhanced binding to E2F DNA-binding sites and cooperative trans-activation of E2F-responsive promoters; the heterodimer is also required for stable interaction with pRB in vivo, and pRB inhibits transcriptional activity of the E2F-1/DP-1 complex. Co-immunoprecipitation (in vivo and in vitro), DNA-binding assays, trans-activation reporter assays Genes & development High 8405995
1993 DP-1 (TFDP1) is a major sequence-specific DNA-binding component of the DRTF1/E2F transcription factor complex, including Rb- and p107-associated forms; its DNA-binding domain resembles that of E2F-1 and recognizes the same sequence. cDNA cloning, DNA-affinity purification, EMSA Nature High 8446173
1993 DP-1 and E2F-1 exist as a heterodimeric DNA-binding complex in vivo, bind preferentially as a heterodimer to the E2F site, and interact synergistically in E2F site-dependent transcriptional activation in yeast and Drosophila cells. Co-immunoprecipitation, EMSA, transcriptional assays in yeast and Drosophila The EMBO journal High 8223441
1994 DP-1 undergoes cell cycle-regulated phosphorylation with a phosphorylation-dependent mobility shift; a C-terminal region of DP-1 interacts with pRb and contributes to pRb binding efficiency in the context of the DP-1/E2F-1 heterodimer; the DP-1/E2F-1 heterodimer specifically interacts with adenovirus E4 orf 6/7 protein to produce cooperative DNA binding at two E2F sites. Immunoprecipitation, phosphopeptide analysis, in vitro binding assays The EMBO journal High 8039504
1994 Cyclin A/CDK2 binds directly to E2F-1 (but not to DP-1) and phosphorylates the E2F-1/DP-1 complex, inhibiting its DNA-binding activity; the complex of cyclin A/CDK2 can be reconstituted from purified components with E2F-1/DP-1. In vitro reconstitution, kinase assay, in vitro and in vivo binding assays, 2D tryptic phosphopeptide mapping Molecular and cellular biology High 7969176
1994 Heterodimerization of E2F-1 and DP-1 is required for stable binding to adenovirus E4 (ORF6/7) protein; pRb binding to E2F-1/DP-1 prevents the formation of an E2F-1/DP-1/E4 complex; the interaction with E4 requires the C-terminal 20 amino acids of E4 and E2F-1 residues 284–358. Co-immunoprecipitation, in vitro binding assays, domain mapping/mutagenesis Journal of virology High 8035503
1994 The hydrophobic heptad repeat domain of DP-1 (amino acids 196–245) mediates heterodimerization with E2F-1's corresponding domain (amino acids 206–283); adenovirus E4 protein directly contacts the DP-1 hydrophobic heptad repeat domain and can dimerize, bridging two E2F-1/DP-1 heterodimers at the E2 promoter. Yeast two-hybrid assay, co-immunoprecipitation, domain mapping Journal of virology High 8207796
1994 The same internal domains of E2F-1 and DP-1 required for E4-6/7 binding are also required for stable interaction with Rb, and E4-6/7 and Rb binding to E2F-1/DP-1 are mutually exclusive. In vitro binding assays, domain deletion mapping Journal of virology High 7933066
1995 MDM2 makes functional contact with both E2F1 and DP1 using residues conserved with the p53 activation domain; in contrast to its repression of p53, MDM2 stimulates the transcriptional activation capacity of E2F1/DP1. Co-immunoprecipitation, transcriptional activation assays, domain mapping Nature High 7791903
1995 E2F-1 and DP-1 physically complex with p53 both in vitro and in vivo; expression of both E2F1 and DP1 can inhibit p53-dependent transcription independently of MDM2, while wild-type p53 can inhibit E2F transcriptional activity. Co-immunoprecipitation, GST pulldown, transcriptional assays The EMBO journal High 8557038
1995 E2F-1/DP-1 co-overexpression leads to greater loss of G1 regulation and significantly more apoptosis than E2F-1 alone; co-expression of DP-1 with E2F-1 increases endogenous p53 levels and overrides survival factors; induction of E2F-1/DP-1 increases expression and activity of cyclins A and E, and CDK2. Inducible expression, flow cytometry, apoptosis assays, immunoblotting Molecular and cellular biology High 8524253
1996 CBP co-activator directly contacts the activation domain of E2F1 both in vitro and in vivo and stimulates E2F1/DP1 transcriptional activity; CBP-induced activation is abolished by E1A N-terminus competitor but not by CBP-binding-deficient E1A mutant. In vitro binding assay, co-immunoprecipitation, transcriptional assays, squelching experiments Nucleic acids research High 8932363
1996 DP-1 mutants that retain E2F binding but lose DNA binding arrest cells in G1 by forming transcriptionally inactive E2F complexes; this G1 arrest can be rescued by co-expression of wild-type E2F or DP; functional domains of DP-1 required for dimerization and DNA binding were separated. Dominant-negative mutant transfection, flow cytometry, rescue experiments Molecular and cellular biology High 8668186
1996 DP-1 associates with p53 in mammalian cell extracts; in vitro p53 interacts with an immunochemically distinct form of DP-1; p53 competes with E2F-1 for DP-1 binding, reducing DNA binding activity; a C-terminal region of DP-1 is required for the interaction with p53, and an N-terminal region of p53 distinct from that required for MDM2 binding is responsible. Co-immunoprecipitation, in vitro binding assays, domain mutagenesis, EMSA Molecular and cellular biology High 8816502
1996 Induction of E2F-1/DP-1 results in increased expression and activity of cyclins A and E, and CDK2 prior to S-phase entry; increased phosphorylation of Rb follows, suggesting E2F feeds back on Rb; DP-1 alone (even with a VP16 transactivation domain) fails to promote cell cycle entry. Inducible expression system, immunoblotting, kinase assays, flow cytometry Cell growth & differentiation High 8780882
1997 p202, an interferon-inducible protein, inhibits E2F-4/DP-1-stimulated transcription; p202 associates with E2F-4 and pocket proteins p107 and p130, and inhibits sequence-specific DNA binding of E2F-4 both in complex with pocket proteins and in its free form. Transcriptional reporter assays, in vitro and in vivo binding assays, EMSA Oncogene Medium 9233764
1998 p53 inhibits transcription driven by the TFDP1 (DP-1) TATA-less promoter at the transcriptional level, with relative specificity for the DP1 promoter compared to the E2F1 promoter or unrelated promoters. Reporter gene assays, promoter deletion analysis The Journal of biological chemistry Medium 9556576
1999 Association of DP-1 with E2F subunits governs intracellular trafficking: DP-1 polypeptides that bind E2F-1 enter the nucleus, whereas those failing to associate with E2F accumulate in the cytoplasm as polyubiquitinated DP-1; E2F-1 binding prevents ubiquitin-dependent cytoplasmic degradation of DP-1. Immunolocalization, immunoprecipitation, cell fractionation, inducible expression Oncogene High 9989809
2001 TRIP-Br1 and TRIP-Br2 proteins contact DP-1 and stimulate E2F-1/DP-1 transcriptional activity; TRIP-Br1 is a component of a multiprotein complex containing E2F-1 and DP-1; KRIP-1 potentiates TRIP-Br co-activation of E2F-1/DP-1; RB abolishes both baseline E2F-1/DP-1 activity and TRIP-Br co-activation. Co-immunoprecipitation, transcriptional assays, protein complex analysis The EMBO journal High 11331592
2001 Deregulated expression of DP-1 in mouse basal layer keratinocytes caused epidermal hyperplasia and hyperproliferation, and enhanced skin carcinogenesis in a two-stage chemical carcinogenesis assay; co-expression with E2F1 or E2F4 modestly enhanced proliferation and apoptosis. Transgenic mouse model, histology, two-stage carcinogenesis assay Molecular carcinogenesis High 11429786
2002 ARF relocalizes DP-1 from the cytoplasm to the nucleolus when DP-1 is alone; however, the E2F1/DP-1 heterodimer is refractory to ARF-induced relocalization and remains in the nucleoplasm; ARF does not interact with the E2F1/DP-1 complex, and E2F1 is more stable in the presence of ARF when co-expressed with DP-1. Immunofluorescence localization, co-immunoprecipitation, stability assays Molecular and cellular biology High 12446760
2003 Loss of Dp1 in mice leads to embryonic lethality due to failure of extra-embryonic (trophectoderm-derived) tissue development; specifically, expansion of the ectoplacental cone and chorion fail, and endoreduplication in trophoblast giant cells is compromised; inactivation of p53 cannot rescue Dp1-deficient embryonic lethality. Dp1 knockout mouse, histology, genetic rescue experiments Development (Cambridge, England) High 12588846
2004 DP-1 activity is required for normal epidermal morphogenesis and ectoderm-to-epidermis transition; dominant-negative DP-1 inhibits E2F/DP-1 heterodimer DNA binding, DNA replication, and cyclin A expression; ChIP showed cyclin A promoter is bound predominantly by E2F-3 and E2F-4 complexes in proliferating keratinocytes. Dominant-negative expression in organotypic culture and embryonic explants, ChIP, immunoblotting The Journal of biological chemistry High 15448153
2004 Dp1-deficient embryonic stem cells can contribute strongly to most chimeric tissues, indicating that Dp1 is largely dispensable for embryonic (but not extraembryonic) development; abundance of DP2 protein does not increase in Dp1-deficient ES cells, and expression of an array of cell cycle genes is virtually unchanged. Chimeric mouse analysis, X-Gal staining, Western blotting, gene expression analysis Molecular and cellular biology High 15282318
2005 The crystal structure of an RbC–E2F1–DP1 complex reveals an intertwined heterodimer in which the marked box domains of both E2F1 and DP1 contact the Rb C-terminal domain (RbC); phosphorylation of RbC at S788/S795 directly destabilizes RbC–E2F/DP interactions, while phosphorylation at T821/T826 induces an intramolecular RbC–Rb pocket interaction that indirectly destabilizes the remaining contacts. X-ray crystallography, biochemical binding assays with phosphorylation-site mutants Cell High 16360038
2005 Two novel isoforms of human DP-1 (DP-1α and DP-1β) were identified; DP-1α lacks a portion of the C-terminal heterodimerization domain, shows significantly reduced binding to E2F1, does not translocate to the nucleus with E2F1, and acts as a dominant-negative regulator causing decreased transcriptional activity and G1 cell cycle arrest. Yeast two-hybrid, immunoprecipitation, immunofluorescence, transcriptional assays, flow cytometry The Journal of biological chemistry High 15863509
2005 ARF directly binds DP-1, and this binding inhibits the interaction between DP-1 and E2F1; ARF regulates DP-1 association with the dhfr target gene promoter (by ChIP); S-phase inhibition by ARF is preceded by inhibition of E2F-activated genes and occurs independently of p53 and Mdm2; the ARF–DP1 interaction is enhanced during oncogenic stress. Direct binding assay (GST pulldown), co-immunoprecipitation, ChIP, cell cycle analysis Molecular and cellular biology High 16135794
2008 SOCS-3 directly interacts with the C-terminal region of DP-1 (requiring SOCS-3 residues 156–172) and is co-localized with DP-1 primarily in the cytoplasm; SOCS-3 inhibits E2F/DP-1 transcriptional activity under the cyclin-E promoter, inhibiting cell cycle progression; conversely, DP-1 almost completely abolishes the inhibitory action of SOCS-3 on JAK-STAT signaling. Yeast two-hybrid, co-immunoprecipitation, confocal microscopy, transcriptional assays, siRNA knockdown The Journal of biological chemistry High 18687693
2010 Cdk5 (in complex with p35) forms a complex with E2F1, excluding DP-1 cofactor from E2F1, thereby inhibiting E2F1 binding to promoters of cell cycle genes and suppressing cell cycle re-entry in post-mitotic neurons; this function does not require Cdk5 enzymatic activity. Co-immunoprecipitation, chromatin immunoprecipitation, kinase-dead mutant analysis The Journal of neuroscience High 20392944
2011 Adenovirus E1A 13S isoform directly binds DP-1 and uses this interaction to recruit itself to E2F-regulated promoters, activating E2F-responsive gene expression independently of pRb-family binding; this binding is through a direct interaction with DP-1 (not E2F), and E1A 13S (but not 12S) enhances E2F4 occupancy at E2F sites. Co-immunoprecipitation, ChIP, reporter assays, domain mapping Journal of virology High 21715488
2015 Kbtbd5 directly interacts with DP-1 (via its dimerization domain) and promotes ubiquitination and degradation of DP-1, thereby inhibiting E2F1-DP-1 transcriptional activity; loss of Kbtbd5 in mice causes increased E2F1 target gene expression and apoptosis in skeletal muscle; breeding into E2F1 null background rescues the lethal phenotype. Yeast two-hybrid, GST pulldown, ubiquitination assay, knockout mouse, genetic epistasis The Journal of biological chemistry High 25940086
2016 COMMD9 interacts with TFDP1 through its COMM domain, requiring the DNA-binding domain of TFDP1; COMMD9 knockdown attenuates TFDP1/E2F1 transcriptional activity and enhances p53 signaling in NSCLC cells. Co-immunoprecipitation, siRNA knockdown, transcriptional assays Cellular signalling Medium 27871936
2016 Knockdown of TFDP1 inhibits E2F1-mediated PITX1 promoter activity and mRNA transcription in articular chondrocytes; E2F1 directly binds GC-rich elements in the PITX1 promoter; TFDP1 knockdown reduces expression of PITX1, BRCA1, CDKN1A, and RAD51 in mid-stage OA chondrocytes. siRNA knockdown, luciferase reporter assay, ChIP, DNA pulldown, qRT-PCR PloS one High 27802335
2019 KPNA2 (karyopherin α2) imports E2F1 and TFDP1 into the nucleus; upon KPNA2 knockdown, E2F1 and TFDP1 are retained in the cytoplasm, leading to reduced STMN1 (stathmin) expression; the KPNA2–E2F1/TFDP1–STMN1 axis regulates tumor cell migration and colony formation in HCC. siRNA knockdown, subcellular fractionation, co-immunoprecipitation, ChIP, proteomics (LC-MS/MS) Cell communication and signaling : CCS High 31783876
2022 KDM6B (an H3K27me3 demethylase) interacts with TFDP1, which normally binds to the promoter of Trp53 to activate Trp53 expression in palatal mesenchymal cells; without KDM6B, TFDP1 cannot activate Trp53, leading to complete cleft palate; H3K27me3 on the Trp53 promoter is antagonistically controlled by KDM6B and EZH2. Conditional knockout mouse, ChIP, co-immunoprecipitation, promoter analysis, histology eLife High 35212626
2023 The TFDP1 gene is a target of deregulated E2F1: overexpression of E2F1 and pRb inactivation (by adenovirus E1a) induce TFDP1 gene expression in normal fibroblasts; deregulated (but not physiological) E2F1 binds GC-rich elements in the TFDP1 promoter (by ChIP); DP1 knockdown enhances ARF gene expression, suggesting TFDP1 induction by deregulated E2F acts as a failsafe feedback mechanism. E2F1 overexpression, adenovirus E1a, promoter deletion analysis, ChIP, shRNA knockdown, qRT-PCR Biochemical and biophysical research communications High 37141667
2024 Genome-wide CRISPR/ATAC-see screening identified TFDP1 as a modulator of global chromatin accessibility; TFDP1 knockout reduces chromatin accessibility by transcriptionally regulating canonical histones. Genome-wide CRISPR screen, ATAC-see, ATAC-seq, TFDP1 knockout Nature genetics High 38361031

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 Heterodimerization of the transcription factors E2F-1 and DP-1 leads to cooperative trans-activation. Genes & development 468 8405995
1995 Stimulation of E2F1/DP1 transcriptional activity by MDM2 oncoprotein. Nature 461 7791903
1994 DRTF1/E2F: an expanding family of heterodimeric transcription factors implicated in cell-cycle control. Trends in biochemical sciences 349 8203017
1994 Cyclin A/CDK2 binds directly to E2F-1 and inhibits the DNA-binding activity of E2F-1/DP-1 by phosphorylation. Molecular and cellular biology 262 7969176
2016 Long non-coding RNA DILC regulates liver cancer stem cells via IL-6/STAT3 axis. Journal of hepatology 256 26812074
1993 A new component of the transcription factor DRTF1/E2F. Nature 256 8446173
1993 Functional synergy between DP-1 and E2F-1 in the cell cycle-regulating transcription factor DRTF1/E2F. The EMBO journal 247 8223441
2005 Structure of the Rb C-terminal domain bound to E2F1-DP1: a mechanism for phosphorylation-induced E2F release. Cell 206 16360038
2002 TFDP1, CUL4A, and CDC16 identified as targets for amplification at 13q34 in hepatocellular carcinomas. Hepatology (Baltimore, Md.) 161 12029633
1995 E2F-1:DP-1 induces p53 and overrides survival factors to trigger apoptosis. Molecular and cellular biology 156 8524253
2005 Prostaglandin D2 mediates neuronal protection via the DP1 receptor. Journal of neurochemistry 141 15659218
2007 The roles of the prostaglandin D(2) receptors DP(1) and CRTH2 in promoting allergic responses. British journal of pharmacology 133 17965752
2012 Binding and activity of the prostacyclin receptor (IP) agonists, treprostinil and iloprost, at human prostanoid receptors: treprostinil is a potent DP1 and EP2 agonist. Biochemical pharmacology 130 22480736
1996 Expression of dominant-negative mutant DP-1 blocks cell cycle progression in G1. Molecular and cellular biology 123 8668186
1996 The CBP co-activator stimulates E2F1/DP1 activity. Nucleic acids research 106 8932363
2017 Targeting the PGD2/CRTH2/DP1 Signaling Pathway in Asthma and Allergic Disease: Current Status and Future Perspectives. Drugs 104 28612233
2001 TRIP-Br: a novel family of PHD zinc finger- and bromodomain-interacting proteins that regulate the transcriptional activity of E2F-1/DP-1. The EMBO journal 102 11331592
2013 Mast cell maturation is driven via a group III phospholipase A2-prostaglandin D2-DP1 receptor paracrine axis. Nature immunology 97 23624557
1994 DP-1: a cell cycle-regulated and phosphorylated component of transcription factor DRTF1/E2F which is functionally important for recognition by pRb and the adenovirus E4 orf 6/7 protein. The EMBO journal 96 8039504
1995 Physical and functional interactions between p53 and cell cycle co-operating transcription factors, E2F1 and DP1. The EMBO journal 92 8557038
1992 Molecular cloning of rat prostate transglutaminase complementary DNA. The major androgen-regulated protein DP1 of rat dorsal prostate and coagulating gland. The Journal of biological chemistry 83 1352290
2010 Cdk5 suppresses the neuronal cell cycle by disrupting the E2F1-DP1 complex. The Journal of neuroscience : the official journal of the Society for Neuroscience 82 20392944
2009 Comprehensive characterization of the DNA amplification at 13q34 in human breast cancer reveals TFDP1 and CUL4A as likely candidate target genes. Breast cancer research : BCR 81 19995430
2007 Hematopoietic prostaglandin D synthase and DP1 receptor are selectively upregulated in microglia and astrocytes within senile plaques from human patients and in a mouse model of Alzheimer disease. Journal of neuropathology and experimental neurology 72 17549007
1997 The lytic enzyme of the pneumococcal phage Dp-1: a chimeric lysin of intergeneric origin. Molecular microbiology 70 9379901
1997 Inhibition of E2F-4/DP-1-stimulated transcription by p202. Oncogene 65 9233764
2020 Loss of DP1 Aggravates Vascular Remodeling in Pulmonary Arterial Hypertension via mTORC1 Signaling. American journal of respiratory and critical care medicine 61 31917615
2002 Differential regulation of E2F1, DP1, and the E2F1/DP1 complex by ARF. Molecular and cellular biology 61 12446760
1996 The molecular basis of E2F-1/DP-1-induced S-phase entry and apoptosis. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 58 8780882
1995 A new member of the DP family, DP-3, with distinct protein products suggests a regulatory role for alternative splicing in the cell cycle transcription factor DRTF1/E2F. Oncogene 57 7478568
2017 Virus-induced inflammasome activation is suppressed by prostaglandin D2/DP1 signaling. Proceedings of the National Academy of Sciences of the United States of America 55 28630327
2003 Dp1 is required for extra-embryonic development. Development (Cambridge, England) 55 12588846
1994 Heterodimerization of the transcription factors E2F-1 and DP-1 is required for binding to the adenovirus E4 (ORF6/7) protein. Journal of virology 54 8035503
1996 Functional interaction between DP-1 and p53. Molecular and cellular biology 53 8816502
2016 COMMD9 promotes TFDP1/E2F1 transcriptional activity via interaction with TFDP1 in non-small cell lung cancer. Cellular signalling 51 27871936
2004 Prostanoid DP1 receptor agonist inhibits the pruritic activity in NC/Nga mice with atopic dermatitis. European journal of pharmacology 51 15556157
2009 Clinical studies of the DP1 antagonist laropiprant in asthma and allergic rhinitis. The Journal of allergy and clinical immunology 50 19748656
2004 Effects of prostaglandin D2, 15-deoxy-Delta12,14-prostaglandin J2, and selective DP1 and DP2 receptor agonists on pulmonary infiltration of eosinophils in Brown Norway rats. The Journal of pharmacology and experimental therapeutics 50 15590767
2003 Association of over-expressed TFDP1 with progression of hepatocellular carcinomas. Journal of human genetics 50 14618416
2020 miR-4711-5p regulates cancer stemness and cell cycle progression via KLF5, MDM2 and TFDP1 in colon cancer cells. British journal of cancer 49 32066912
2014 Prostaglandin D2 and the role of the DP1, DP2 and TP receptors in the control of airway reflex events. The European respiratory journal 47 25323233
2010 Genome annotation and intraviral interactome for the Streptococcus pneumoniae virulent phage Dp-1. Journal of bacteriology 46 21097633
2016 A novel alkaline keratinase from Bacillus subtilis DP1 with potential utility in cosmetic formulation. International journal of biological macromolecules 43 26940376
2022 DP1 (Prostaglandin D2 Receptor 1) Activation Protects Against Vascular Remodeling and Vascular Smooth Muscle Cell Transition to Myofibroblasts in Angiotensin II-Induced Hypertension in Mice. Hypertension (Dallas, Tex. : 1979) 42 35354317
2011 Adenovirus E1A directly targets the E2F/DP-1 complex. Journal of virology 42 21715488
2005 ARF directly binds DP1: interaction with DP1 coincides with the G1 arrest function of ARF. Molecular and cellular biology 42 16135794
2007 PGD(2) DP1 receptor protects brain from ischemia-reperfusion injury. The European journal of neuroscience 41 17573924
2010 Gene amplification of the transcription factor DP1 and CTNND1 in human lung cancer. The Journal of pathology 36 20556744
2010 Mast cell-derived prostaglandin D2 controls hyaluronan synthesis in human orbital fibroblasts via DP1 activation: implications for thyroid eye disease. The Journal of biological chemistry 35 20308056
2019 Long noncoding RNA lnc-DILC stabilizes PTEN and suppresses clear cell renal cell carcinoma progression. Cell & bioscience 34 31592114
2019 Karyopherin α2-dependent import of E2F1 and TFDP1 maintains protumorigenic stathmin expression in liver cancer. Cell communication and signaling : CCS 34 31783876
2019 LncRNA DILC participates in rheumatoid arthritis by inducing apoptosis of fibroblast-like synoviocytes and down-regulating IL-6. Bioscience reports 33 30944206
2014 Dexamethasone protects neonatal hypoxic-ischemic brain injury via L-PGDS-dependent PGD2-DP1-pERK signaling pathway. PloS one 33 25474649
2010 Prostaglandin D2 DP1 receptor is beneficial in ischemic stroke and in acute exicitotoxicity in young and old mice. Age (Dordrecht, Netherlands) 33 20640551
1995 Functional conservation of the cell cycle-regulating transcription factor DRTF1/E2F and its pathway of control in Drosophila melanogaster. Journal of cell science 33 8537434
2020 Inhibition of lncRNA DILC attenuates neuropathic pain via the SOCS3/JAK2/STAT3 pathway. Bioscience reports 31 32510145
1994 Interacting domains of E2F1, DP1, and the adenovirus E4 protein. Journal of virology 31 8207796
2020 DP1 Activation Reverses Age-Related Hypertension Via NEDD4L-Mediated T-Bet Degradation in T Cells. Circulation 30 31893939
1994 Mutually exclusive interaction of the adenovirus E4-6/7 protein and the retinoblastoma gene product with internal domains of E2F-1 and DP-1. Journal of virology 30 7933066
2019 Structure of the DP1-DP2 PolD complex bound with DNA and its implications for the evolutionary history of DNA and RNA polymerases. PLoS biology 28 30657780
2019 lncRNA DILC is downregulated in osteoarthritis and regulates IL-6 expression in chondrocytes. Journal of cellular biochemistry 28 31069838
2018 The endogenous bioactive lipid prostaglandin D2-glycerol ester reduces murine colitis via DP1 and PPARγ receptors. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 28 29630407
1996 Expression of the E2F-1/DP-1 transcription factor in murine development. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 28 8788032
2018 Long non-coding RNA DILC suppresses cell proliferation and metastasis in colorectal cancer. Gene 27 29621586
2001 Deregulated expression of DP1 induces epidermal proliferation and enhances skin carcinogenesis. Molecular carcinogenesis 27 11429786
2018 Prostaglandin D2 Receptor DP1 Antibodies Predict Vaccine-induced and Spontaneous Narcolepsy Type 1: Large-scale Study of Antibody Profiling. EBioMedicine 26 29449194
2019 Role of the L-PGDS-PGD2-DP1 receptor axis in sleep regulation and neurologic outcomes. Sleep 24 30893431
2011 Co-operative signalling through DP(1) and DP(2) prostanoid receptors is required to enhance leukotriene C(4) synthesis induced by prostaglandin D(2) in eosinophils. British journal of pharmacology 24 20973774
2004 Characterization of the 3' exonuclease subunit DP1 of Methanococcus jannaschii replicative DNA polymerase D. Nucleic acids research 24 15121900
2004 The DP-1 transcription factor is required for keratinocyte growth and epidermal stratification. The Journal of biological chemistry 24 15448153
1998 The p53 tumor suppressor inhibits transcription of the TATA-less mouse DP1 promoter. The Journal of biological chemistry 24 9556576
1984 Biochemical characterization of a murein hydrolase induced by bacteriophage Dp-1 in Streptococcus pneumoniae: comparative study between bacteriophage-associated lysin and the host amidase. Journal of bacteriology 24 6146601
2008 Central prostaglandin D(2) exhibits anxiolytic-like activity via the DP(1) receptor in mice. Prostaglandins & other lipid mediators 23 19007903
2007 Rubimetide (Met-Arg-Trp) derived from Rubisco exhibits anxiolytic-like activity via the DP1 receptor in male ddY mice. Peptides 23 18243414
1983 A phage-associated murein hydrolase in Streptococcus pneumoniae infected with bacteriophage Dp-1. Journal of general microbiology 23 6132961
2005 Identification and characterization of novel isoforms of human DP-1: DP-1{alpha} regulates the transcriptional activity of E2F1 as well as cell cycle progression in a dominant-negative manner. The Journal of biological chemistry 22 15863509
2004 Dp1 is largely dispensable for embryonic development. Molecular and cellular biology 22 15282318
1995 Regulation of transcription by E2F1/DP1. Journal of cell science. Supplement 22 8655653
1999 Association with E2F-1 governs intracellular trafficking and polyubiquitination of DP-1. Oncogene 21 9989809
2019 Long non-coding RNA DILC promotes the progression of gallbladder carcinoma. Gene 20 30716440
2016 E2F1 and TFDP1 Regulate PITX1 Expression in Normal and Osteoarthritic Articular Chondrocytes. PloS one 20 27802335
2008 SOCS-3 inhibits E2F/DP-1 transcriptional activity and cell cycle progression via interaction with DP-1. The Journal of biological chemistry 20 18687693
1993 Regulation of adenovirus 12 E1A transcription: E2F and ATF motifs in the E1A promoter bind nuclear protein complexes including E2F1, DP-1, cyclin A and/or RB and mediate transcriptional (auto)activation. Cellular & molecular biology research 20 7951410
2023 The TFDP1 gene coding for DP1, the heterodimeric partner of the transcription factor E2F, is a target of deregulated E2F. Biochemical and biophysical research communications 19 37141667
2010 Potent and highly selective DP1 antagonists with 2,3,4,9-tetrahydro-1H-carbazole as pharmacophore. Bioorganic & medicinal chemistry letters 19 21036609
2000 Differential cytotoxic pathways of topoisomerase I and II anticancer agents after overexpression of the E2F-1/DP-1 transcription factor complex. Clinical cancer research : an official journal of the American Association for Cancer Research 19 10778981
2018 Long non‑coding RNA DILC is involved in sepsis by modulating the signaling pathway of the interleukin‑6/signal transducer and activator of transcription 3/Toll‑like receptor 4 axis. Molecular medicine reports 18 30365067
2017 A randomized controlled phase II clinical trial comparing ONO-4053, a novel DP1 antagonist, with a leukotriene receptor antagonist pranlukast in patients with seasonal allergic rhinitis. Allergy 18 28378369
2024 Genome-wide ATAC-see screening identifies TFDP1 as a modulator of global chromatin accessibility. Nature genetics 17 38361031
2022 KDM6B interacts with TFDP1 to activate P53 signaling in regulating mouse palatogenesis. eLife 17 35212626
2016 mTOR regulates proteasomal degradation and Dp1/E2F1- mediated transcription of KPNA2 in lung cancer cells. Oncotarget 17 27009856
2015 Effect of the potent and selective DP1 receptor antagonist, asapiprant (S-555739), in animal models of allergic rhinitis and allergic asthma. European journal of pharmacology 17 26277322
2013 Inverse agonist and pharmacochaperone properties of MK-0524 on the prostanoid DP1 receptor. PloS one 17 23762421
1997 The predominant E2F complex in human primary haemopoietic cells and in AML blasts contains E2F-4, DP-1 and p130. British journal of haematology 17 9074408
2021 Protectin DX promotes the inflammatory resolution via activating COX-2/L-PGDS-PGD2 and DP1 receptor in acute respiratory distress syndrome. International immunopharmacology 16 34920958
2012 Nicotinic acid and DP1 blockade: studies in mouse models of atherosclerosis. Journal of lipid research 16 23103473
2018 DP1 receptor signaling prevents the onset of intrinsic apoptosis in eosinophils and functions as a transcriptional modulator. Journal of leukocyte biology 15 29607536
2015 Kelch Repeat and BTB Domain Containing Protein 5 (Kbtbd5) Regulates Skeletal Muscle Myogenesis through the E2F1-DP1 Complex. The Journal of biological chemistry 15 25940086
2014 PGD2 DP1 receptor stimulation following stroke ameliorates cerebral blood flow and outcomes. Neuroscience 15 25218962
2006 Effects of TS-022, a newly developed prostanoid DP1 receptor agonist, on experimental pruritus, cutaneous barrier disruptions and atopic dermatitis in mice. European journal of pharmacology 15 17141215