HUMAN ADENOVIRUS - A GLIMPSE ON APOPTOSIS AND CANCER

Products of the E1A gene of human adenoviruses induce both expression of other viral genes and DNA synthesis to allow viral replication in t erminally differentiated epithelial target cells. However, E1A product s also cause an increase in the cellular p53 protein and the induction of apoptosis by a p53-dependent pathway. This response would prevent adequate production of progeny virions in human cells and block transf ormation of rodent cells which fail to replicate virus. The viral E1B gene encodes two products which inhibit this process, a 55 kDa protein which binds to and inactivates p53, and a 19 kDa species which blocks apoptosis in a fashion similar to the cellular Bcl-2 cell death suppr essor. We have shown recently that adenoviruses also induce p53-indepe ndent apoptosis in a process which requires expression of one or more E4 proteins. The E4 region encodes at least seven proteins which, in a ddition to cell killing, are involved in regulation. of gene expressio n and control of p53. As was the case previously with RNA splicing. tr anscription, DNA synthesis and oncogenesis, the study of adenovirus pr oducts is providing new insights into another important cell function, apoptosis, and may offer the possibility of new therapeutics in the t reatment of human cancer.