Wild-type p53 induction mediated by replication-deficient adenoviral vectors

Replication-deficient E1-/E3-deleted adenoviral vectors are commonly used t o introduce transgenes into cells in vitro and have been used for certain k inds of gene therapy protocols in vivo. We have demonstrated that transduct ion of cells using these vectors can induce p53 expression in cells contain ing a wild-type p53 gene. This response is different from p53 induction obs erved after DNA damage because the time course of induction is slower and b ecause it occurs in cells with an attenuated DNA damage response. However, this vector-induced p53 is transcriptionally active and, therefore, p53 fun ction is not inactivated by viral proteins. The mechanism of induction appe ars to be an increased rate of protein translation because immunoprecipitat ion analyses demonstrated increased levels of S-35-labeled p53 protein, eve n after a short 15-min labeling time. Induction of p53 by adenoviral vector s may have various effects on transduced cells, including apoptosis and alt ered chemotherapy chemosensitivity. Therefore, the influence of the vector might confound the impact of any particular gene used in a gene therapy app lication.