title: The adenovirus E1A 289R and 243R proteins inhibit the phosphorylation of p300.
abstract: A protein of 300 kDa (p300) associates with the adenovirus E1A proteins and has been implicated in the control of cell cycle progression. In mammalian cells, p300 is actively phosphorylated in both quiescent and proliferating cells and its level of phosphorylation increases as it travels from late G1 into M phase. E1A requires p300 for the induction of cellular DNA synthesis and the repression of enhancer mediated transcription, suggesting that p300 may be involved in pathways that are important to cell proliferation and gene expression. Since the activities of most cell cycle regulatory proteins depend on their phosphorylation state, the possibility exists that certain activities of p300 might also be controlled by phosphorylation and that E1A might in fact be affecting these events. We show here by in vitro analysis that E1A inhibits the phosphorylation of p300 by decreasing the rate of incorporation of phosphate into p300. We also show that p300 can be used as a substrate for the cyclin-dependent p33cdk2 and p34cdc2 kinases, and propose that E1A might be antagonistic to these enzymes in phosphorylating p300. Thus, these results indicate a possible novel function by which E1A can interfere with cellular pathways.
authors.affiliation: Department of Molecular Biology, Cleveland Clinic Foundation, Ohio 44195.
authors.forename: A C
authors.initials: AC
authors.lastname: Banerjee
authors.forename: A J
authors.initials: AJ
authors.lastname: Recupero
authors.forename: A
authors.initials: A
authors.lastname: Mal
authors.forename: A M
authors.initials: AM
authors.lastname: Piotrkowski
authors.forename: D M
authors.initials: DM
authors.lastname: Wang
authors.forename: M L
authors.initials: ML
authors.lastname: Harter
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D017500:Adenovirus E1A Proteins / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation
chemical_list: D017500:Adenovirus E1A Proteins; D009687:Nuclear Proteins; D000255:Adenosine Triphosphate; D004247:DNA