CLONING OF A BCL-2 HOMOLOG BY INTERACTION WITH ADENOVIRUS E1B 19K

NUMBER Of DNA viruses carry apoptosis-inhibiting genes which enable th e virus to escape from the host reponse(1-5). The adenovirus E1B 19K p rotein can inhibit apoptosis induced by E1A, tumour-necrosis factor-al pha, FAS antigen and nerve growth factor deprivation(6-9). The molecul ar basis of this inhibition remains poorly understood, but the fact th at protection is seen in the absence of other viral proteins suggests that E1B 19K targets cellular proteins. We report here the identificat ion of three cellular proteins that bind E1B 19K, One of these is a ne w member of the bcl-2 family(10-16), which we have called bak (for bcl -2 homologous antagonist/killer). This protein, which is expressed in a wide variety of cell types, binds to E1B 19K and to the Bcl-2 homolo gue Bcl-x(L) (ref, 17) in yeast, In addition, overexpression of bak in sympathetic neurons deprived of nerve growth factor accelerates apopt osis and blocks the protective effect of co-injected E1B 19K.