Association of p300 and CBP with simian virus 40 large T antigen.
p300 and the CREB-binding protein CBP are two large nuclear phosphoproteins that are structurally highly related. Both function, in part, as transcriptional adapters and are targeted by the adenovirus E1A oncoprotein. We show here that p300 and CBP interact with another transforming protein, the simian virus 40 large T antigen (T). This interaction depends on the integrity of a region of T which is critical for its transforming and mitogenic properties and includes its LXCXE Rb-binding motif. T interferes with normal p300 and CBP function on at least two different levels. The presence of T alters the phosphorylation states of both proteins and inhibits their transcriptional activities on certain promoters. Although E1A and T show little sequence similarity, they interact with the same domain of p300 and CBP, suggesting that this region exhibits considerable flexibility in accommodating diverse protein ligands.
Eckner
R
R
Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Ludlow
J W
JW
Lill
N L
NL
Oldread
E
E
Arany
Z
Z
Modjtahedi
N
N
DeCaprio
J A
JA
Livingston
D M
DM
Morgan
J A
JA
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D000952:Antigens, Polyomavirus Transforming / Q000302:isolation & purification / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D015153:Blotting, Western; D050882:CREB-Binding Protein; D002455:Cell Division; D050881:E1A-Associated p300 Protein; D004591:Electrophoresis, Polyacrylamide Gel; D004622:Embryo, Mammalian; D005347:Fibroblasts; D005982:Glutathione Transferase; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D015534:Trans-Activators; D014157:Transcription Factors / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D014162:Transfection
D000906:Antibodies; D000952:Antigens, Polyomavirus Transforming; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse; D005982:Glutathione Transferase