Distinct Modulation of p53 Activity in Transcription and Cell-Cycle Regulation by the Large (54 kDa) and Small (21 kDa) Adenovirus E1B Proteins

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• 作者：Steegenga ; Wilma T. ; Van Laar ; Theo ; Shvarts ; Avi ; Terleth ; Carrol ; Van Der Eb ; Alex J. ; Jochemsen ; A. G.
• 刊名：Virology
• 出版年：1995
• 出版时间：October 1, 1995
• 年：1995
• 卷：212
• 期：2
• 页码：543-554
• 全文大小：824 K

文摘

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.