Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor.
The growth-controlling functions of the adenovirus E1A oncoprotein depend on its ability ot interact with a set of cellular proteins. Among these are the retinoblastoma protein, p107, p130, and p300. We have isolated a cDNA encoding full-length human p300 and mapped the chromosomal location of the gene to chromosome 22q13. p300 contains three cysteine- and histidine-rich regions of which the most carboxy-terminal region interacts specifically with E1A. In its center, p300 contains a bromodomain, a hallmark of certain transcriptional coactivators. We have examined the ability of p300 to overcome the repressive effect of E1A on the SV40 enhancer. We show that p300 molecules lacking an intact E1A-binding site can bypass E1A repression and restore to a significant extent the activity of the SV40 enhancer, even in the presence of high levels of E1A protein. These results imply that p300 may function as a transcriptional adaptor protein for certain complex transcriptional regulatory elements.
Eckner
R
R
Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Ewen
M E
ME
Newsome
D
D
Gerdes
M
M
DeCaprio
J A
JA
Lawrence
J B
JB
Livingston
D M
DM
D017500:Adenovirus E1A Proteins / Q000378:metabolism*; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002451:Cell Compartmentation; D002453:Cell Cycle / Q000235:genetics; D002478:Cells, Cultured; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D050881:E1A-Associated p300 Protein; D004742:Enhancer Elements, Genetic / Q000235:genetics; D000939:Epitopes; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000096:biosynthesis; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013539:Simian virus 40 / Q000235:genetics; D015534:Trans-Activators; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic
D017500:Adenovirus E1A Proteins; D018076:DNA, Complementary; D000939:Epitopes; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050881:E1A-Associated p300 Protein