| 1993 |
DP-1 (TFDP1) and E2F-1 heterodimerize both in vivo and in vitro, enhancing binding to E2F DNA-binding sites and leading to cooperative trans-activation of E2F-responsive promoters. This heterodimerization is also required for stable interaction with pRb in vivo, and pRb inhibits trans-activation by E2F-1/DP-1 heterodimers. |
Co-immunoprecipitation (in vivo), in vitro binding assay, reporter gene trans-activation assays |
Genes & development |
High |
8405995
|
| 1993 |
DP-1 is a major sequence-specific DNA-binding protein component of DRTF1/E2F, present in Rb- and p107-associated forms. Its DNA-binding domain resembles that of E2F-1 and recognizes the same sequence. |
Protein purification from E2F DNA-affinity column, cDNA isolation, DNA binding assays |
Nature |
High |
8446173
|
| 1993 |
DP-1 and E2F-1 exist in a DNA-binding complex in vivo, binding efficiently and 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, transcription assays in yeast and Drosophila |
The EMBO journal |
High |
8223441
|
| 1994 |
DP-1 is a phosphoprotein that undergoes a phosphorylation-dependent mobility shift during cell cycle progression. A C-terminal region of DP-1 interacts with pRb and, in the context of the DP-1/E2F-1 heterodimer, contributes to the efficiency of pRb binding. The DP-1/E2F-1 heterodimer specifically interacts with adenovirus type 5 E4 orf 6/7 protein to produce a cooperative DNA-binding activity. |
Cell fractionation, phosphorylation analysis, co-immunoprecipitation, EMSA, deletion mutant binding assays |
The EMBO journal |
High |
8039504
|
| 1994 |
Cyclin A/CDK2 directly binds E2F-1 (but not DP-1) and phosphorylates E2F-1 in vitro and in vivo, inhibiting the DNA-binding activity of the E2F-1/DP-1 complex. The cyclin A/CDK2-binding region resides within the N-terminal 124 amino acids of E2F-1. |
In vitro kinase assay, co-immunoprecipitation, 2D tryptic phosphopeptide mapping, deletion mutant binding, DNA binding assay |
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. This binding is DNA-independent and requires the C-terminal 20 amino acids of E4 and a region of E2F-1 between amino acids 284 and 358. Importantly, pRb binding to the E2F-1/DP-1 heterodimer prevents formation of the E2F-1/DP-1/E4 complex, and the same internal segments of E2F-1 and DP-1 are required for both E4-6/7 and Rb binding. |
Co-immunoprecipitation, deletion mutant binding assays |
Journal of virology |
High |
7933066 8035503
|
| 1992 |
Cyclin A recruits the CDK subunit p33cdk2 to the DRTF1/E2F transcription factor complex (which contains DP-1), activating histone H1 kinase activity within the complex. Cyclin A cannot direct p34cdc2 to the DRTF1 complex. |
Biologically active fusion protein binding assays, histone H1 kinase assay, co-immunoprecipitation |
Journal of cell science. Supplement |
Medium |
1297652
|
| 1995 |
Co-expression of DP-1 and E2F-1 results in greater loss of G1 regulation and significantly more apoptosis than E2F-1 alone. Induction of E2F-1/DP-1 resulted in increased expression and activity of cyclins A and E, as well as CDK2, prior to S-phase entry; cyclin D and CDK4 were not induced. E2F-1/DP-1 also increases pRb phosphorylation, suggesting a feedback on pRb. |
Inducible expression system, flow cytometry, Western blotting, kinase assays, apoptosis assays |
Cell growth & differentiation |
Medium |
8780882
|
| 1995 |
E2F-1:DP-1 co-overexpression overrides survival factor (IL-3) signaling to trigger rapid apoptosis, and augments p53 levels. DP-1 alone is insufficient to induce cell cycle progression or alter death rates, but cooperates with E2F-1 to induce apoptosis and p53 accumulation. |
Overexpression in IL-3-dependent myeloid cells, flow cytometry, Western blotting, apoptosis assays |
Molecular and cellular biology |
Medium |
8524253
|
| 1996 |
Expression of dominant-negative DP-1 mutants that retain E2F dimerization but lack DNA binding arrests cells in G1, forming transcriptionally inactive E2F complexes. This G1 arrest can be rescued by co-expression of wild-type E2F or DP protein, establishing that active E2F/DP-1 complexes are required for cell cycle progression. |
Dominant-negative DP-1 mutant transfection, flow cytometry, domain mapping |
Molecular and cellular biology |
High |
8668186
|
| 1996 |
DP-1 directly 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, reducing DNA-binding activity. A C-terminal region of DP-1 is required for p53 interaction; a distinct N-terminal region of p53 (different from MDM2-binding region) mediates this. |
Co-immunoprecipitation in vivo and in vitro, competitive binding assays, deletion mutant analysis, reporter assays |
Molecular and cellular biology |
Medium |
8816502
|
| 1995 |
A Drosophila DP protein interacts co-operatively with E2F proteins as a physiological DNA-binding component of Drosophila DRTF1/E2F. The DRTF1/E2F pathway features (interaction with pocket proteins, binding to cyclin A and cdk2, modulation by viral oncoproteins) are conserved in Drosophila. |
Co-immunoprecipitation, DNA binding assay, transcriptional assays in Drosophila cells |
Journal of cell science |
Medium |
8537434
|
| 1999 |
Association with E2F subunits governs intracellular trafficking and polyubiquitination of DP-1. DP-1 mutants that stably bind E2F-1 enter the nucleus, whereas DP-1 proteins that fail to associate with E2F accumulate in the cytoplasm as polyubiquitinated DP-1, subject to proteasomal degradation. |
Immunolocalization, co-immunoprecipitation, cell fractionation, transient transfection, conditional expression cell line |
Oncogene |
Medium |
9989809
|
| 2001 |
TRIP-Br1/TRIP-Br2 proteins interact with DP-1 (similar to MDM2's homologous transactivation domain), stimulating E2F-1/DP-1 transcriptional activity. TRIP-Br1 is a component of a multiprotein complex containing E2F-1 and DP-1. Co-expression of Rb abolishes this co-activation, which is restored by adenovirus E1A. |
Yeast two-hybrid, co-immunoprecipitation, reporter assays, cell fractionation |
The EMBO journal |
Medium |
11331592
|
| 2003 |
Loss of protein phosphatase 2A (PP2A) expression correlates with the appearance of a phosphorylated, slower-mobility form of DP-1 associated with cellular differentiation and reversal of dysplasia. Persistent PP2A expression prevents the phosphorylated form of DP-1 required for differentiation. |
Conditional mouse model, Western blot mobility shift analysis, immunohistochemistry |
Cancer research |
Low |
14633688
|
| 2004 |
DP-1 activity is required for normal epidermal morphogenesis and keratinocyte growth. Expression of dominant-negative DP-1 (dnDP-1) inhibits E2F/DP-1 heterodimer DNA binding, blocks DNA replication, decreases cyclin A expression, and disrupts epidermal stratification. Chromatin immunoprecipitation showed the cyclin A promoter is bound by E2F-3/E2F-4-containing DP-1 complexes in proliferating keratinocytes. |
Dominant-negative expression, organotypic culture, embryonic ectoderm explants, ChIP, Western blotting |
The Journal of biological chemistry |
Medium |
15448153
|
| 2005 |
Two novel DP-1 isoforms (DP-1α, DP-1β) were identified. DP-1α lacks a portion of the C-terminal heterodimerization domain, has significantly reduced E2F-1 binding, fails to translocate to the nucleus with E2F-1, and acts as a dominant-negative regulator of cell cycle progression, decreasing E2F transcriptional activity and inhibiting cell proliferation. |
Yeast two-hybrid, co-immunoprecipitation, immunofluorescence, reporter assays, flow cytometry |
The Journal of biological chemistry |
Medium |
15863509
|
| 2008 |
SOCS-3 interacts with the C-terminal region of DP-1 (residues 156–172 of SOCS-3 required); they co-localize primarily in the cytoplasm. SOCS-3 inhibits E2F/DP-1 transcriptional activity and cell cycle progression by interfering with DP-1/E2F heterodimer formation. Reciprocally, DP-1 inhibits SOCS-3-mediated suppression of JAK-STAT signaling. |
Yeast two-hybrid, co-immunoprecipitation, confocal microscopy, reporter assays, siRNA knockdown |
The Journal of biological chemistry |
Medium |
18687693
|
| 2010 |
A C-terminal acidic 'Stabilon' domain of DP-1 is critical for protein stability; removal of this domain leads to degradation. Wild-type DP-1 is degraded by the ubiquitin-proteasome system, and the Stabilon is identified as key for preventing this degradation. |
Deletion mutant analysis, Western blotting, proteasome inhibitor assays |
Biochemical and biophysical research communications |
Low |
20513349
|
| 2011 |
Adenovirus E1A 13S isoform directly binds DP-1 (not pRb) to activate E2F-responsive gene expression. E1A recruits itself to E2F-regulated promoters through this direct DP-1 interaction, and E1A 13S (but not 12S) significantly enhances E2F4 occupancy at E2F sites. |
Co-immunoprecipitation, chromatin immunoprecipitation, reporter assays, mutant E1A constructs |
Journal of virology |
Medium |
21715488
|
| 2013 |
Somatic missense, nonsense, and frameshift mutations in DP-1 (TFDP1) are identified in human tumors. Most mutations leave dimerization intact but alter DNA binding, transcriptional activation, and pRb-binding properties of the E2F-1/DP-1 heterodimer via a transdominant mechanism; many mutants impair E2F-1-dependent apoptosis. |
Genomic database mining, functional assays (DNA binding, transcription, pRb binding, apoptosis) with mutant DP-1 constructs |
Oncogene |
Medium |
23934193
|
| 2016 |
COMMD9 physically interacts with TFDP1 through its COMM domain, requiring the DNA-binding domain of TFDP1 for this interaction. COMMD9 promotes TFDP1/E2F1 transcriptional activity; knockdown of COMMD9 attenuates TFDP1/E2F1 activation, arrests the cell cycle at G1/S, and inhibits proliferation in NSCLC cells. |
Co-immunoprecipitation, siRNA knockdown, reporter assays, cell cycle analysis |
Cellular signalling |
Medium |
27871936
|
| 2016 |
E2F1 and TFDP1 form a complex that directly regulates PITX1 transcription in articular chondrocytes. TFDP1 knockdown inhibits the activating effect of E2F1 and reduces both PITX1 promoter activity and mRNA transcription. ChIP assays confirmed direct E2F1-PITX1 promoter binding. |
Luciferase reporter assay, chromatin immunoprecipitation, siRNA knockdown, DNA pulldown |
PloS one |
Medium |
27802335
|
| 2019 |
KPNA2 (karyopherin α2) mediates nuclear import of E2F1 and TFDP1. Upon KPNA2 knockdown, E2F1 and TFDP1 are retained in the cytoplasm, resulting in reduced STMN1 (stathmin) expression, decreased tumor cell migration, and reduced colony formation in HCC cells. |
Co-immunoprecipitation, subcellular fractionation, ChIP, quantitative proteomics (LC-MS/MS), siRNA knockdown, colony formation assay |
Cell communication and signaling : CCS |
Medium |
31783876
|
| 2022 |
KDM6B (an H3K27me3 demethylase) specifically interacts with TFDP1 to activate Trp53 expression in palatal mesenchymal cells. Without KDM6B, TFDP1 cannot activate Trp53 expression. KDM6B antagonistically controls H3K27me3 on the Trp53 promoter with EZH2; TFDP1 normally binds the Trp53 promoter. |
Conditional knockout mouse model, ChIP, reporter assays, co-immunoprecipitation |
eLife |
Medium |
35212626
|
| 2023 |
The TFDP1 gene is a transcriptional target of deregulated E2F1. Overexpression of E2F1 and forced pRb inactivation (by adenovirus E1a) induces TFDP1 gene expression. GC-rich elements in the TFDP1 promoter bind deregulated (but not physiological) E2F1 as shown by ChIP. DP-1 knockdown enhances ARF expression (a deregulated E2F target), suggesting a failsafe feedback mechanism. |
Reporter assay (promoter deletion and point mutation analysis), ChIP, shRNA knockdown, adenovirus E1a overexpression |
Biochemical and biophysical research communications |
Medium |
37141667
|
| 2024 |
TFDP1 modulates global chromatin accessibility through transcriptional regulation of canonical histones. CRISPR knockout of TFDP1 revealed distinct and specific effects on chromatin accessibility genome-wide. |
Genome-wide CRISPR screen combined with ATAC-see, ATAC-seq, TFDP1 knockout |
Nature genetics |
High |
38361031
|
| 2024 |
TFDP1 is essential for HSPC proliferation and post-transplant hematopoiesis. E2F4 serves as a binding partner of TFDP1 in HSPCs, and deletion of TFDP1 causes downregulation of cell cycle genes, approximately 50% of which are direct targets of TFDP1 and E2F4. |
In vivo CRISPR/Cas9-based genetic screen, bone marrow transplantation, gene expression analysis, ChIP (direct target identification) |
Leukemia |
High |
39043964
|
| 2021 |
An E2F5-TFDP1-BRG1 complex mediates transcriptional activation of MYCN in hepatocytes during liver regeneration. BRG1 is recruited by E2F5/TFDP1 to the MYCN promoter and regulates histone H3 acetylation and H3K4 trimethylation to facilitate RNA polymerase II binding. |
RNA interference, ChIP, co-immunoprecipitation, qPCR, Western blotting |
Frontiers in cell and developmental biology |
Medium |
34746136
|
| 2002 |
Antisense oligonucleotide-mediated downregulation of TFDP1 in HCC cells led to downregulation of CCNE1, indicating that TFDP1 overexpression drives upregulation of CCNE1 (a positive regulator of G1/S transition). |
Antisense oligonucleotide knockdown, quantitative real-time PCR |
Hepatology (Baltimore, Md.) |
Low |
12029633
|
| 2003 |
Antisense-mediated down-regulation of TFDP1 in Hep3B HCC cells (which overexpress TFDP1) inhibited cell growth, and expression of TFDP1 and E2F1 correlated with expression of seven transcriptional targets (TYMS, DHFR, PCNA, RRM1, CCNE1, CDC2, MYBL2) playing roles in G1/S transition. |
Antisense oligonucleotide knockdown, quantitative real-time RT-PCR, cell growth assay |
Journal of human genetics |
Low |
14618416
|
| 2015 |
Positional cloning of the medaka kyoho mutant identified TFDP1 as the causative gene; loss of TFDP1 leads to S-phase arrest and higher polyploidization of erythrocytes, resulting in abnormally large erythrocytes with altered karyotype during development. |
Positional cloning, phenotypic analysis of mutant fish, cell cycle analysis |
Developmental dynamics |
Medium |
25648602
|
| 2014 |
A recurrent frameshift indel mutation (indel84) in TFDP1 found in 70% of colorectal cancers generates an alternative TFDP1 protein missing the first 120 amino acids (including the DNA-binding domain) and confers a gain-of-function phenotype: increased cell proliferation, migration, and invasion of CRC cells. |
Next-generation sequencing, functional assays (proliferation, migration, invasion) with mutant TFDP1 |
Omics : a journal of integrative biology |
Medium |
25133581
|
| 2023 |
TFDP1 transcriptionally activates TK1 (thymidine kinase 1) in cervical cancer cells by directly binding to the TK1 promoter. TFDP1 knockdown suppresses TK1 expression and reduces cervical cancer cell proliferation, EMT, migration, and invasion, and TK1 overexpression rescues the suppressive effects of TFDP1 knockdown. |
Chromatin immunoprecipitation, dual-luciferase reporter assay, siRNA knockdown, rescue experiments, xenograft |
Functional & integrative genomics |
Medium |
37715794
|
| 2024 |
TFDP1 transcriptionally activates SPC25, and TFDP1-SPC25 signaling promotes glutamine metabolism in lung adenocarcinoma cells to suppress NK cell anti-tumor immunity. ChIP and luciferase reporter assays confirmed TFDP1 as a direct transcriptional activator of SPC25. |
Luciferase reporter assay, ChIP, flow cytometry, LDH cytotoxicity assay, ELISA |
Expert review of clinical immunology |
Low |
40552366
|
| 2025 |
TFDP1 inhibits cellular senescence in TNBC cells; its knockdown inhibits cell growth, clonal expansion, and tumorigenicity. Topotecan inhibits TNBC cell growth and promotes senescence, counteracting the effects of TFDP1 overexpression, suggesting TFDP1 is a functional target of topotecan. |
CRISPR/Cas9 library screen, knockdown, overexpression, senescence assays, cell growth assays, xenograft |
International journal of biological macromolecules |
Low |
40300683
|