transcription factor dp1


Summary: A transcription factor that possesses DNA-binding and E2F-binding domains but lacks a transcriptional activation domain. It is a binding partner for E2F TRANSCRIPTION FACTORS and enhances the DNA binding and transactivation function of the DP-E2F complex.

Top Publications

  1. Chellappan S, Hiebert S, Mudryj M, Horowitz J, Nevins J. The E2F transcription factor is a cellular target for the RB protein. Cell. 1991;65:1053-61 pubmed
  2. Sørensen T, Girling R, Lee C, Gannon J, Bandara L, La Thangue N. Functional interaction between DP-1 and p53. Mol Cell Biol. 1996;16:5888-95 pubmed
    ..Our results establish DRTF1/E2F as a common cellular target in growth control mediated through the activities of pRb and p53 and suggest an alternative mechanism through which p53 may regulate cellular proliferation. ..
  3. Girling R, Partridge J, Bandara L, Burden N, Totty N, Hsuan J, et al. A new component of the transcription factor DRTF1/E2F. Nature. 1993;365:468 pubmed
  4. Lees J, Saito M, Vidal M, Valentine M, Look T, Harlow E, et al. The retinoblastoma protein binds to a family of E2F transcription factors. Mol Cell Biol. 1993;13:7813-25 pubmed
    ..These observations suggest that the E2F activities described previously result from the combined action of a family of proteins. ..
  5. Halaban R, Cheng E, Zhang Y, Mandigo C, Miglarese M. Release of cell cycle constraints in mouse melanocytes by overexpressed mutant E2F1E132, but not by deletion of p16INK4A or p21WAF1/CIP1. Oncogene. 1998;16:2489-501 pubmed
    ..Thus, mechanisms other than the loss of p16INK4A or p21WAF1/CIP1 that activate E2F may play an important role in melanomas. ..
  6. Holmberg C, Helin K, Sehested M, Karlstrom O. E2F-1-induced p53-independent apoptosis in transgenic mice. Oncogene. 1998;17:143-55 pubmed
    ..Testicular atrophy as a result of overexpression of E2F-1 and DP-1 is independent of functional p53, since p53-nullizygous transgenic mice overexpressing E2F-1 and DP-1 also suffered testicular atrophy. ..
  7. Qiao H, Di Stefano L, Tian C, Li Y, Yin Y, Qian X, et al. Human TFDP3, a novel DP protein, inhibits DNA binding and transactivation by E2F. J Biol Chem. 2007;282:454-66 pubmed
    ..In conclusion, these studies identify a new DP protein and a novel mechanism whereby E2F function is regulated. ..
  8. Nevins J. The Rb/E2F pathway and cancer. Hum Mol Genet. 2001;10:699-703 pubmed
    ..Questions remain, however, as to the specific role played by individual activities within the pathway in the control of cell growth and their participation in the development of cancer. ..
  9. Magae J, Wu C, Illenye S, Harlow E, Heintz N. Nuclear localization of DP and E2F transcription factors by heterodimeric partners and retinoblastoma protein family members. J Cell Sci. 1996;109 ( Pt 7):1717-26 pubmed
    ..These results indicate that DP proteins preferentially associate with specific E2F partners, and suggest that the ability of specific E2F/DP heterodimers to localize in the nucleus contributes to the regulation of E2F activity. ..

More Information


  1. Ohtani K, DeGregori J, Leone G, Herendeen D, Kelly T, Nevins J. Expression of the HsOrc1 gene, a human ORC1 homolog, is regulated by cell proliferation via the E2F transcription factor. Mol Cell Biol. 1996;16:6977-84 pubmed
    ..These results thus provide a direct link between the initiation of DNA replication and the cell growth regulatory pathway involving G1 cyclin-dependent kinases, the Rb tumor suppressor, and E2F. ..
  2. Karlseder J, Rotheneder H, Wintersberger E. Interaction of Sp1 with the growth- and cell cycle-regulated transcription factor E2F. Mol Cell Biol. 1996;16:1659-67 pubmed
    ..Our data are in line with the hypothesis that E2F functions as a growth- and cell cycle regulated tethering factor between Sp1 and the basic transcription machinery. ..
  3. Field S, Tsai F, Kuo F, Zubiaga A, Kaelin W, Livingston D, et al. E2F-1 functions in mice to promote apoptosis and suppress proliferation. Cell. 1996;85:549-61 pubmed
    ..These findings suggest that while certain members of the E2F family may positively regulate cell cycle progression, E2F-1 functions to regulate apoptosis and to suppress cell proliferation. ..
  4. Ikeda M, Jakoi L, Nevins J. A unique role for the Rb protein in controlling E2F accumulation during cell growth and differentiation. Proc Natl Acad Sci U S A. 1996;93:3215-20 pubmed
    ..These results suggest that the specific ability of Rb protein to interact with each E2F species, dependent on concentration of active Rb relative to accumulation of E2F, may be critical in cell-growth decisions. ..
  5. Lindeman G, Gaubatz S, Livingston D, Ginsberg D. The subcellular localization of E2F-4 is cell-cycle dependent. Proc Natl Acad Sci U S A. 1997;94:5095-100 pubmed
    ..Thus, the subcellular location of E2F-4 is regulated in a cell cycle-dependent manner, providing another potential mechanism for its functional regulation. ..
  6. Kohn M, Leung S, Criniti V, Agromayor M, Yamasaki L. Dp1 is largely dispensable for embryonic development. Mol Cell Biol. 2004;24:7197-205 pubmed
    ..5 tissues with the absence of Dp1. Thus, Dp1 is largely dispensable for embryonic development, despite the absolute extraembryonic requirement for Dp1, which is highly reminiscent of the restricted roles for Rb and cyclins E1/E2 in vivo. ..
  7. Ginsberg D, Vairo G, Chittenden T, Xiao Z, Xu G, Wydner K, et al. E2F-4, a new member of the E2F transcription factor family, interacts with p107. Genes Dev. 1994;8:2665-79 pubmed
    ..p107 binding not only can be linked to the regulation of E2F-4 transcriptional activity, but also to suppression of the ability of E2F-4 to transform an immortalized rodent cell line. ..
  8. Lukas J, Herzinger T, Hansen K, Moroni M, Resnitzky D, Helin K, et al. Cyclin E-induced S phase without activation of the pRb/E2F pathway. Genes Dev. 1997;11:1479-92 pubmed
    ..They furthermore indicate that a lack of E2F-mediated transactivation can be compensated by hyperactivation of this cyclin E-controlled event. ..
  9. Yamada M, Kondo T, Ashizawa S, Takebayashi T, Higashi H, Hatakeyama M. Role of pRB-family/E2F complex in the inhibition of IL-3-dependent lymphoid cell proliferation. Cytokine. 2002;17:91-7 pubmed
    ..Our results indicate that blocking E2F-dependent transactivation, but not the formation of p130-E2F transcriptional repressor complexes, is responsible for the inhibition of IL-3-dependent cell growth by p130. ..
  10. Dagnino L, Fry C, Bartley S, Farnham P, Gallie B, Phillips R. Expression patterns of the E2F family of transcription factors during murine epithelial development. Cell Growth Differ. 1997;8:553-63 pubmed
    ..Thus, selective regulation of E2F forms occurs during murine epithelial development, irrespective of the ectodermal or endodermal origin of such epithelia. ..
  11. Kohn M, Bronson R, Harlow E, Dyson N, Yamasaki L. Dp1 is required for extra-embryonic development. Development. 2003;130:1295-305 pubmed
    ..Thus, DP1 is absolutely required for extra-embryonic development and consequently embryonic survival, consistent with E2F/DP1 normally acting to promote growth in vivo. ..
  12. Yasui K, Arii S, Zhao C, Imoto I, Ueda M, Nagai H, et al. TFDP1, CUL4A, and CDC16 identified as targets for amplification at 13q34 in hepatocellular carcinomas. Hepatology. 2002;35:1476-84 pubmed
    ..In conclusion, our findings suggest that TFDP1, CUL4A, and CDC16 are probable targets of an amplification mechanism and therefore may be involved, together or separately, in development and/or progression of some HCCs. ..
  13. Magae J, Illenye S, Chang Y, Mitsui Y, Heintz N. Association with E2F-1 governs intracellular trafficking and polyubiquitination of DP-1. Oncogene. 1999;18:593-605 pubmed
    ..Our studies indicate association with E2F subunits prevents ubiquitin-dependent degradation of DP-1 in the cytoplasm by promoting nuclear entry of E2F/DP heterodimers. ..
  14. Lundberg A, Weinberg R. Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes. Mol Cell Biol. 1998;18:753-61 pubmed
    ..Complete phosphorylation of pRb, inactivation of E2F binding, and activation of E2F transcription occur only after sequential action of at least two distinct G1 cyclin kinase complexes. ..
  15. Tiainen M, Spitkovsky D, Jansen Durr P, Sacchi A, Crescenzi M. Expression of E1A in terminally differentiated muscle cells reactivates the cell cycle and suppresses tissue-specific genes by separable mechanisms. Mol Cell Biol. 1996;16:5302-12 pubmed
    ..Our results show that E1A reactivates the cell cycle and suppresses tissue-specific gene expression in terminally differentiated muscle cells, thus causing dedifferentiation. ..
  16. Weinberg R. The retinoblastoma protein and cell cycle control. Cell. 1995;81:323-30 pubmed
  17. Zhu L, Xie E, Chang L. Differential roles of two tandem E2F sites in repression of the human p107 promoter by retinoblastoma and p107 proteins. Mol Cell Biol. 1995;15:3552-62 pubmed
    ..Interestingly, the repression was found to be mediated through the 5' copy of the E2F site. These studies demonstrate for the first time differential roles of two tandem E2F sites in promoter regulation. ..
  18. Neuman E, Flemington E, Sellers W, Kaelin W. Transcription of the E2F-1 gene is rendered cell cycle dependent by E2F DNA-binding sites within its promoter. Mol Cell Biol. 1994;14:6607-15 pubmed
    ..Thus, E2F-1 appears to be regulated at the level of transcription, and this regulation is due, at least in part, to binding of one or more E2F family members to the E2F-1 promoter. ..
  19. Castillo S, Angulo B, Suarez Gauthier A, Melchor L, Medina P, Sanchez Verde L, et al. Gene amplification of the transcription factor DP1 and CTNND1 in human lung cancer. J Pathol. 2010;222:89-98 pubmed publisher
    ..TFDP1, which encodes the E2F-associated transcription factor DP1 is a candidate oncogene at 13q34...
  20. Rubin S, Gall A, Zheng N, Pavletich N. Structure of the Rb C-terminal domain bound to E2F1-DP1: a mechanism for phosphorylation-induced E2F release. Cell. 2005;123:1093-106 pubmed
    ..Our findings explain the requirement of RbC for high-affinity E2F binding and growth suppression and establish a mechanism for the regulation of Rb-E2F association by phosphorylation. ..
  21. Datta A, Sen J, Hagen J, Korgaonkar C, Caffrey M, Quelle D, et al. ARF directly binds DP1: interaction with DP1 coincides with the G1 arrest function of ARF. Mol Cell Biol. 2005;25:8024-36 pubmed
    ..Also, the interaction between ARF and DP1 is enhanced during oncogenic stress and "culture shock." Taken together, our results show that DP1 is a critical direct target of ARF. ..
  22. Corbeil H, Whyte P, Branton P. Characterization of transcription factor E2F complexes during muscle and neuronal differentiation. Oncogene. 1995;11:909-20 pubmed
    ..These results suggested that in both muscle and neurons, pRB and p130 may play specific roles in the development or maintenance of terminal differentiation. ..
  23. Yasui K, Okamoto H, Arii S, Inazawa J. Association of over-expressed TFDP1 with progression of hepatocellular carcinomas. J Hum Genet. 2003;48:609-13 pubmed
    ..In conclusion, overexpression of TFDP1 may contribute to progression of some HCCs by promoting growth of the tumor cells. ..
  24. Hiebert S, Chellappan S, Horowitz J, Nevins J. The interaction of RB with E2F coincides with an inhibition of the transcriptional activity of E2F. Genes Dev. 1992;6:177-85 pubmed
    ..A mutant pRB protein that does not associate with E2F does not inhibit transcription. We conclude that as a consequence of its interaction with E2F, pRB may regulate the transcriptional function of the E2F factor. ..
  25. Brehm A, Miska E, McCance D, Reid J, Bannister A, Kouzarides T. Retinoblastoma protein recruits histone deacetylase to repress transcription. Nature. 1998;391:597-601 pubmed
    ..Our results indicate that histone deacetylases are important for regulating the cell cycle and that active transcriptional repression by Rb may involve the modification of chromatin structure. ..
  26. Johnson D, Cress W, Jakoi L, Nevins J. Oncogenic capacity of the E2F1 gene. Proc Natl Acad Sci U S A. 1994;91:12823-7 pubmed
    ..Cells transfected with E2F1 and DP1 or the E2F1-VP16 chimera form colonies in soft agar and induce tumor formation in nude mice. We conclude that deregulated E2F1 expression and function can have oncogenic consequences. ..
  27. Di Fiore B, Guarguaglini G, Palena A, Kerkhoven R, Bernards R, Lavia P. Two E2F sites control growth-regulated and cell cycle-regulated transcription of the Htf9-a/RanBP1 gene through functionally distinct mechanisms. J Biol Chem. 1999;274:10339-48 pubmed
    ..Thus, the two E2F sites play opposite genetic functions and control RanBP1 transcription through distinct molecular mechanisms. ..
  28. Halaban R. Melanoma cell autonomous growth: the Rb/E2F pathway. Cancer Metastasis Rev. 1999;18:333-43 pubmed
    ..Since all pocket proteins are regulated by CDKs activity, it is likely that agents that inhibit this class of enzymes will be effective in treating melanoma patients. ..
  29. Dyson N. The regulation of E2F by pRB-family proteins. Genes Dev. 1998;12:2245-62 pubmed
  30. Yee A, Shih H, Tevosian S. New perspectives on retinoblastoma family functions in differentiation. Front Biosci. 1998;3:D532-47 pubmed
    ..The collective observations hypothesize the existence of a differentiation checkpoint to insure fidelity. ..
  31. Ishida H, Masuhiro Y, Fukushima A, Argueta J, Yamaguchi N, Shiota S, et al. 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. J Biol Chem. 2005;280:24642-8 pubmed
    ..Together, the results of the present study suggest that DP-1alpha is a novel isoform of DP-1 that acts as a dominant-negative regulator of cell cycle progression. ..
  32. Takahashi Y, Rayman J, Dynlacht B. Analysis of promoter binding by the E2F and pRB families in vivo: distinct E2F proteins mediate activation and repression. Genes Dev. 2000;14:804-16 pubmed
    ..These findings suggest that repression and activation of E2F-responsive genes may occur through distinct E2F heterodimers that direct the sequential recruitment of enzymes able to deacetylate and then acetylate core histones. ..
  33. Wu C, Zukerberg L, Ngwu C, Harlow E, Lees J. In vivo association of E2F and DP family proteins. Mol Cell Biol. 1995;15:2536-46 pubmed
    ..However, the various E2F/DP complexes display strong differences in the ability to bind to either pRB or p107 in vivo, and the specificity of pRB or p107 binding is mediated by the E2F subunit. ..
  34. Lavia P, Jansen Durr P. E2F target genes and cell-cycle checkpoint control. Bioessays. 1999;21:221-30 pubmed
    ..It is also clear that deregulation of E2F activity will result in the loss of particular checkpoint controls, thereby predisposing cells to malignant conversion. ..
  35. Welch P, Wang J. Disruption of retinoblastoma protein function by coexpression of its C pocket fragment. Genes Dev. 1995;9:31-46 pubmed
    ..These results suggest that the inhibition of RB-binding proteins is not sufficient to suppress cell growth and that the assembly of RB-mediated protein complexes is also important for the promotion of cell-cycle arrest. ..
  36. Pierce A, Gimenez Conti I, Schneider Broussard R, Martinez L, Conti C, Johnson D. Increased E2F1 activity induces skin tumors in mice heterozygous and nullizygous for p53. Proc Natl Acad Sci U S A. 1998;95:8858-63 pubmed
    ..These findings firmly establish that increased E2F1 expression can contribute to tumor development and suggest that p53 plays an important role in eliminating cells with deregulated E2F1 activity. ..
  37. Johnson D, Ohtani K, Nevins J. Autoregulatory control of E2F1 expression in response to positive and negative regulators of cell cycle progression. Genes Dev. 1994;8:1514-25 pubmed
  38. Magnaghi Jaulin L, Groisman R, Naguibneva I, Robin P, Lorain S, Le Villain J, et al. Retinoblastoma protein represses transcription by recruiting a histone deacetylase. Nature. 1998;391:601-5 pubmed
    ..Our results strongly suggest that the Rb/HDAC1 complex is a key element in the control of cell proliferation and differentiation and that it is a likely target for transforming viruses. ..
  39. Dagnino L, Fry C, Bartley S, Farnham P, Gallie B, Phillips R. Expression patterns of the E2F family of transcription factors during mouse nervous system development. Mech Dev. 1997;66:13-25 pubmed
    ..We conclude that individual E2F forms are differentially regulated during the development of distinct tissues, and especially during neuronal development. ..
  40. Cobrinik D, Lee M, Hannon G, Mulligan G, Bronson R, Dyson N, et al. Shared role of the pRB-related p130 and p107 proteins in limb development. Genes Dev. 1996;10:1633-44 pubmed
    ..Thus, in certain settings p107 and p130 perform growth-regulatory functions that are not fulfilled by pRB. ..
  41. Helin K, Harlow E, Fattaey A. Inhibition of E2F-1 transactivation by direct binding of the retinoblastoma protein. Mol Cell Biol. 1993;13:6501-8 pubmed
    ..In conclusion, these data demonstrate that pRB inhibits E2F-dependent transactivation by direct protein-protein interaction. ..
  42. Muller H, Moroni M, Vigo E, Petersen B, Bartek J, Helin K. Induction of S-phase entry by E2F transcription factors depends on their nuclear localization. Mol Cell Biol. 1997;17:5508-20 pubmed
  43. Chan J, Olvera M, Lai R, Naing W, Rezk S, Brynes R. Immunohistochemical expression of the transcription factor DP-1 and its heterodimeric partner E2F-1 in non-Hodgkin lymphoma. Appl Immunohistochem Mol Morphol. 2002;10:322-6 pubmed
  44. Zhang H, Postigo A, Dean D. Active transcriptional repression by the Rb-E2F complex mediates G1 arrest triggered by p16INK4a, TGFbeta, and contact inhibition. Cell. 1999;97:53-61 pubmed
    ..Thus, a major role of E2F in cell cycle regulation is assembly of this repressor complex. We demonstrate that active repression by Rb-E2F mediates the G1 arrest triggered by TGFbeta, p16INK4a, and contact inhibition. ..
  45. Cartwright P, Muller H, Wagener C, Holm K, Helin K. E2F-6: a novel member of the E2F family is an inhibitor of E2F-dependent transcription. Oncogene. 1998;17:611-23 pubmed
    ..Our data suggest that E2F-6 expression delays the exit from S-phase rather than inducing S-phase, which further emphasizes the functional difference between E2F-6 and the previously known E2F family members. ..
  46. Datta A, Nag A, Raychaudhuri P. Differential regulation of E2F1, DP1, and the E2F1/DP1 complex by ARF. Mol Cell Biol. 2002;22:8398-408 pubmed
  47. Ferreira R, Magnaghi Jaulin L, Robin P, Harel Bellan A, Trouche D. The three members of the pocket proteins family share the ability to repress E2F activity through recruitment of a histone deacetylase. Proc Natl Acad Sci U S A. 1998;95:10493-8 pubmed
    ..Taken together, our data suggest that all members of the E2F family are regulated in early G1 by similar complexes, containing a pocket protein and the histone deacetylase HDAC1. ..
  48. Hsiao K, McMahon S, Farnham P. Multiple DNA elements are required for the growth regulation of the mouse E2F1 promoter. Genes Dev. 1994;8:1526-37 pubmed
    ..However, the E2F sites are not sufficient to mediate growth-regulated transcriptional activity; our results indicate that multiple DNA elements are required for transcription regulation of the E2F1 promoter at the G1/S-phase boundary. ..
  49. Harbour J, Luo R, Dei Santi A, Postigo A, Dean D. Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1. Cell. 1999;98:859-69 pubmed
    ..Cdk4/6 is activated early in G1, blocking active repression by Rb. However, it is not until near the end of G1, when cyclin E is expressed and Cdk2 is activated, that Rb is prevented from binding and inactivating E2F. ..
  50. Mudryj M, Devoto S, Hiebert S, Hunter T, Pines J, Nevins J. Cell cycle regulation of the E2F transcription factor involves an interaction with cyclin A. Cell. 1991;65:1243-53 pubmed
    ..We suggest that these interactions control the activity of E2F and that disruption of the complexes by E1A contributes to a loss of cellular proliferation control. ..
  51. Ohtani K, Tsujimoto A, Ikeda M, Nakamura M. Regulation of cell growth-dependent expression of mammalian CDC6 gene by the cell cycle transcription factor E2F. Oncogene. 1998;17:1777-85 pubmed
  52. Beijersbergen R, Kerkhoven R, Zhu L, Carlee L, Voorhoeve P, Bernards R. E2F-4, a new member of the E2F gene family, has oncogenic activity and associates with p107 in vivo. Genes Dev. 1994;8:2680-90 pubmed
    ..We show that expression of E2F-4 and DP-1 together with an activated ras oncogene in rat embryo fibroblasts, causes transformation, indicating that E2F-4 has oncogenic activity. ..
  53. Botz J, Zerfass Thome K, Spitkovsky D, Delius H, Vogt B, Eilers M, et al. Cell cycle regulation of the murine cyclin E gene depends on an E2F binding site in the promoter. Mol Cell Biol. 1996;16:3401-9 pubmed
    ..An E2F binding site which is required for G1-specific activation of the cyclin E promoter in synchronized NIH 3T3 cells was identified in this fragment. ..