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PMID: 8039504 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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 ·Vol. 13 ·No. 13 ·1994-07-01 ·Pages 3104-14

Bandara LR, Lam EW, Sørensen TS, Zamanian M, Girling R, La Thangue NB

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.

MeSH Terms
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
Chemicals
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
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Bandara L R
Laboratory of Eukaryotic Molecular Genetics, MRC National Institute for Medical Research, London, UK.
Lam E W
Sørensen T S
Zamanian M
Girling R
La Thangue N B
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1994-07-01
Pages
3104-14
Language
English
Region
England
NLM ID
8208664
PMCID
PMC395201
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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