DP forms a heterodimer with E2F and regulates genes involved in cell cycle progression. The transcriptional activity of E2F is inhibited by the retinoblastoma protein which binds to the E2F-DP heterodimer [(PUBMED:16360038)] and negatively regulates the G1-S transition.
The transcription factor DP (dimerization partner) forms a heterodimer with E2F and regulates genes involved in cell cycle progression. The transcriptional activity of E2F is inhibited by the retinoblastoma protein which binds to the E2F-DP heterodimer [ (PUBMED:16360038) ] and negatively regulates the G1-S transition.
Though originally the role of DP in transcriptional activation was thought to be facilitating the binding of E2F to target DNA, it was latter shown that the C-terminal acidic region of DP1 binds strongly to the PH domain of p62 of TFIIH. and acts as a transactivation domain [ (PUBMED:27825926) ].
Family alignment:
There are 1503 DP domains in 1502 proteins in SMART's nrdb database.
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Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing DP domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with DP domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing DP domain in the selected taxonomic class.
Structure of the Rb C-terminal domain bound to E2F1-DP1: a mechanism forphosphorylation-induced E2F release.
Cell. 2005; 123: 1093-106
Display abstract
The retinoblastoma (Rb) protein negatively regulates the G1-S transition bybinding to the E2F transcription factors, until cyclin-dependent kinasesphosphorylate Rb, causing E2F release. The Rb pocket domain is necessary for E2F binding, but the Rb C-terminal domain (RbC) is also required for growthsuppression. Here we demonstrate a high-affinity interaction between RbC andE2F-DP heterodimers shared by all Rb and E2F family members. The crystalstructure of an RbC-E2F1-DP1 complex reveals an intertwined heterodimer in which the marked box domains of both E2F1 and DP1 contact RbC. We also demonstrate thatphosphorylation of RbC at serines 788 and 795 destabilizes one set of RbC-E2F-DP interactions directly, while phosphorylation at threonines 821 and 826 induces anintramolecular interaction between RbC and the Rb pocket that destabilizes theremaining interactions indirectly. Our findings explain the requirement of RbCfor high-affinity E2F binding and growth suppression and establish a mechanismfor the regulation of Rb-E2F association by phosphorylation.
In vivo association of E2F and DP family proteins.
Mol Cell Biol. 1995; 15: 2536-46
Display abstract
The mammalian transcription factor E2F plays an important role in regulating the expression of genes that are required for passage through the cell cycle. Thistranscriptional activity is inhibited by association with the retinoblastomatumor suppressor protein (pRB) or its relatives p107 and p103. The first cDNAfrom the E2F family to be cloned was designated E2F-1, and multiple E2F familymembers have now been identified. They bind to DNA as heterodimers, interactingwith proteins known as DP. Here we demonstrate that DP is also a family ofpolypeptides with at least two members (hDP-1 and hDP-2). Both hDP-1 and hDP-2bind to all E2F family members in vivo, and each complex is capable of activatingtranscription. However, the various E2F/DP complexes display strong differencesin 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.
