DISTINCT MODULATION OF P53 ACTIVITY IN TRANSCRIPTION AND CELL-CYCLE REGULATION BY THE LARGE (54 KDA) AND SMALL (21 KDA) ADENOVIRUS E1B PROTEINS

P53 can both stimulate transcription via the p53-consensus sequence as well as inhibit gene expression via CAAT-TATA-sequences. Certain viral and cellular proteins can abrogate the p53-dependent stimulation of transcription by physical association. In addition, it has been shown that the large E1B protein of adenovirus type 12 (Ad12), E1b/54 kDa, can block the transcription activation potential of p53, without binding to p53. Here we show that this E1B/54-kDa protein also can prevent the repression of transcription by transfected and endogenous p53 in transient transfections. In cells containing wild-type p53 but stably expressing high levels of E1B/54 kDa, no induction of WAF1 mRNA after X-ray irradiation could be detected. In contrast, expression of another non-p53 binding E1B protein, Ad5 E1B/21 kDa has no effect on WAF1 expression. Results of an electromobility shift assay indicated that the abrogation of p53-mediated transcription activation by E1B/54 kDa cannot be explained by inhibition of the DNA-binding capacity of p53. A biological consequence of expression of E1B/54 kDa is the loss of G1 cell-cycle arrest after X-ray irradiation, while cells expressing the E1B/21 kDa still arrest in G1 after DNA damage. (C) 1995 Academic Press, Inc.