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.

Abstract	The cellular transcription factor DRTF1/E2F integrates cell cycle events with the transcription apparatus through its cyclical interactions with important regulators of cellular proliferation. Two sequence-specific DNA binding proteins, DP-1 and E2F-1, are components of DRTF1/E2F which synergistically interact in a DP-1/E2F-1 heterodimer. Here, we show that DP-1 is a very frequent, possibly universal, component of DRTF1/E2F in 3T3 cells since it is present in all forms of the DNA binding activity that occur during cell cycle progression. Furthermore, the DP-1 polypeptide, which is phosphorylated, undergoes a phosphorylation-dependent mobility shift during the cell cycle suggesting that its level of phosphorylation is regulated during cell cycle progression. A C-terminal region in DP-1 can interact with pRb which, 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 the adenovirus type 5 E4 orf 6/7 protein, to produce a DNA binding activity which binds co-operatively to, and transcriptionally activates through, two appropriately positioned E2F sites in a manner which resembles the regulation of DRTF1/E2F by E4 orf 6/7 during adenovirus infection. We conclude that DP-1 is a frequent and cell cycle-regulated component of DRTF1/E2F, and that in the DP-1/E2F-1 heterodimer it is functionally important for recognition by pRb and the E4 orf 6/7 protein.
Authors	L R Bandara, E W Lam, T S Sørensen, M Zamanian, R Girling, N B La Thangue
Journal	The EMBO journal (EMBO J) Vol. 13 Issue 13 Pg. 3104-14 (Jul 01 1994) ISSN: 0261-4189 [Print] England
PMID	8039504 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Activating Transcription Factor 2 Adenovirus E4 Proteins Arid4a protein, mouse Carrier Proteins Cell Cycle Proteins Cyclic AMP Response Element-Binding Protein DNA, Viral DNA-Binding Proteins Dp transcription factor, Drosophila Drosophila Proteins E2F Transcription Factors E2F1 Transcription Factor E2f1 protein, mouse Recombinant Fusion Proteins Retinoblastoma Protein Retinoblastoma-Binding Protein 1 Tfdp1 protein, mouse Trans-Activators Transcription Factor DP1 Transcription Factors
Topics	3T3 Cells Activating Transcription Factor 2 Adenovirus E4 Proteins (metabolism) Animals Carrier Proteins Cell Cycle (physiology) Cell Cycle Proteins Cell Line Cyclic AMP Response Element-Binding Protein (metabolism) DNA, Viral (metabolism) DNA-Binding Proteins (chemistry, metabolism) Drosophila Drosophila Proteins E2F Transcription Factors E2F1 Transcription Factor Mice Models, Biological Mutation Phosphorylation Protein Binding Protein Conformation Recombinant Fusion Proteins (metabolism) Retinoblastoma Protein (genetics, metabolism) Retinoblastoma-Binding Protein 1 Trans-Activators Transcription Factor DP1 Transcription Factors (chemistry, metabolism) Transcriptional Activation

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