THE ADENOVIRUS-E1A 12S PRODUCT DISPLAYS FUNCTIONAL REDUNDANCY IN ACTIVATING THE HUMAN PROLIFERATING CELL NUCLEAR ANTIGEN PROMOTER

The adenovirus E1A 243R oncoprotein stimulates expression from the promoter of the human proliferating cell nuclear antigen (PCNA). To gain insight into the mechanism of activation, we analyzed deletion and point mutations of the 243R protein for their abilities to activate PCNA promoter-directed reporter gene expression upon cotransfection into HeLa cells. Large deletions that in combination span the entire protein severely impaired the ability of EIA 243R to induce PCNA expression. Smaller deletions and specific point mutations that target specific E1A-binding proteins were less deleterious to PCNA induction. The data suggest that E1A activates transcription of the PCNA gene by multiple mechanisms and that, of the known 243R-associated proteins, p300 and p107-cyclin A can mediate the response while p105-RB does not appear to participate. Presumably, the functional redundancy ensures that 243R can activate expression of this essential DNA replication protein regardless of cell type and physiological conditions.