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

NUMBER Of DNA viruses carry apoptosis-inhibiting genes which enable the virus to escape from the host reponse(1-5). The adenovirus E1B 19K protein can inhibit apoptosis induced by E1A, tumour-necrosis factor-alpha, FAS antigen and nerve growth factor deprivation(6-9). The molecular basis of this inhibition remains poorly understood, but the fact that protection is seen in the absence of other viral proteins suggests that E1B 19K targets cellular proteins. We report here the identification of three cellular proteins that bind E1B 19K, One of these is a new 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 homologue Bcl-x(L) (ref, 17) in yeast, In addition, overexpression of bak in sympathetic neurons deprived of nerve growth factor accelerates apoptosis and blocks the protective effect of co-injected E1B 19K.