CONTROL OF PROGRAMMED CELL-DEATH BY THE BACULOVIRUS GENES P35 AND IAP

The SF-21 insect tell line undergoes rapid and widespread apoptosis when treated with actinomycin D or when infected,vith a mutant of the baculovirus Autographa californica nuclear polyhedrosis virus lacking a p35 gene or a functionally active lap (inhibitor of apoptosis) gene. Here we provide evidence that the basis far the induction of apoptosis by these two different stimuli is the cessation of RNA synthesis. We also show that expression of either p35 or two different functional lap homologs blocks apoptosis independently of other viral genes, indicating that these gene products act directly on the cellular apoptotic pathway. The lap genes encode a C3HC4 (or RING) finger motif found in a number of transcriptional regulatory proteins, as well as two additional Cys/His motifs (baculovirus lap repeats). We show that specific amino acids, within both the C3HC4 finger and the N-terminal baculovirus lap repeat are critical for antiapoptosis function. Overexpression of either mammalian bcl-2 or adenovirus E1B-19K, genes which block apoptosis when overexpressed in a number of mammalian cells, does not block actinomycin D induced apoptosis in SF-21 tells.