Adenoviral E1A-associated protein p300 as a functional homologue of the transcriptional co-activator CBP.
The 265K nuclear protein CBP was initially identified as a co-activator for the protein kinase A (PKA)-phosphorylated form of the transcription factor CREB. The domains in CBP that are involved in CREB binding and transcriptional activation are highly related to the adenoviral E1A-associated cellular protein p300 (refs 2, 3), and to two hypothetical proteins from Caenorhabditis elegans, R10E11.1 and K03H1.10 (refs 4 and 5, respectively), whose functions are unknown. Here, we show that CBP and p300 have similar binding affinity for the PKA-phosphorylated form of CREB, and that p300 can substitute for CBP in potentiating CREB-activated gene expression. We find that E1A binds to CBP through a domain conserved with p300 and represses the CREB-dependent co-activator functions of both CBP and p300. Our results indicate that the gene repression and cell immortalization functions associated with E1A involve the inactivation of a family of related proteins that normally participate in second-messenger-regulated gene expression.
Lundblad
J R
JR
Vollum Institute, Oregon Health Sciences University, Portland 97201.
Kwok
R P
RP
Laurance
M E
ME
Harter
M L
ML
Goodman
R H
RH
D017500:Adenovirus E1A Proteins / Q000378:metabolism*; D000595:Amino Acid Sequence; D050882:CREB-Binding Protein; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D050881:E1A-Associated p300 Protein; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D017500:Adenovirus E1A Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050882:CREB-Binding Protein; D050881:E1A-Associated p300 Protein; D017868:Cyclic AMP-Dependent Protein Kinases