Interaction of cellular apoptosis regulating proteins with adenovirus anti-apoptosis protein E1B-19K.

Abstract

Human adenoviruses have been excellent models for gene expression in mammalian cells. They have also been very important tools in dissecting complex cellular processes such as control of cell proliferation, oncogenesis, and apoptosis. The adenovirus genome contains 36 kb of linear double-stranded DNA that is organized as early and late genes. The left 14% of the viral genome contains two early gene regions, E1A and E1B, that encode proteins that mediate oncogenic transformation of cultured cells and regulate apoptosis. The E1A region codes for two major proteins of 289 amino acids (289R) and 243 amino acids (243R). The E1A proteins are sufficient to immortalize and partially transform primary rodent cells in vitro (). The E1B region codes for two major proteins of 55K (496R) and 19K (175R), which cooperate with E1A in transformation individually (,). A major function of E1A is induction of proliferation of quiescent host cells to facilitate viral replication. The unscheduled synthesis of cellular DNA initiated by E1A expression also leads to apoptosis. Both E1B proteins suppress apoptosis induced by E1A. One of the consequences of E1A expression is elevation of expression of the tumor suppressor protein p53 (). The 55K protein appears to mediate its anti-apoptosis activity primarily by binding to p53 and antagonizing the activity of p53. On the other hand, the E1B-19K protein exhibits a more general antiapoptosis activity and efficiently suppresses apoptosis induced by a multitude of stimuli and is a functional homolog of the cellular anti-apoptosis protein BCL-2 (, , ).