CH-IAP1, A MEMBER OF THE INHIBITOR-OF-APOPTOSIS PROTEIN FAMILY, IS A MEDIATOR OF THE ANTIAPOPTOTIC ACTIVITY OF THE V-REL ONCOPROTEIN

The oncoprotein v-Rel, a member of the Rel/NF-kappa B family of transc ription factors, induces neoplasias and inhibits apoptosis, To identif y differentially regulated cellular genes and to evaluate their releva nce to transformation and apoptosis in v-Rel-transformed cells, mRNA d ifferential display has been used, One of the recovered cDNAs correspo nds to a gene that was highly expressed in v-Rel-transformed fibroblas ts. Analysis of the isolated full-length cDNA of a chicken inhibitor-o f-apoptosis protein (ch-IAP1) revealed that it encodes a 68-kDa protei n that is highly homologous to members of the IAP family, such as huma n c-IAP1. Like other IAPs, ch-IAP1 contains the N-terminal baculovirus IAP repeats and C-terminal RING finger motifs, Northern blot analysis identified a 3.3-kb ch-IAP1 transcript: expressed at relatively high levels in the spleen, thymus, bursa, intestine, and lungs, Expression if v-Rel in fibroblasts, a B-cell line, and spleen cells up-regulated the expression of ch-IAP1. In contrast, ch-IAP1 expression levels were low in chicken cell limes transformed by several other unrelated tumo r viruses, ch-IAP1 was expressed predominantly in the cytoplasm of the v-Rel-transformed cells, ch-IAP1 suppressed mammalian cell apoptosis induced by the overexpression of the interleukin-1-converting enzyme. Expression of exogenous ch-IAP1 in temperature-sensitive v-Rel transfo rmed spleen cells inhibited apoptosis of these cells at the nonpermiss ive temperature. Collectively, these results suggest that. ch-IAP1 is induced during the v-Rel-mediated transformation process and functions as a suppressor of apoptosis in v-Rel-transformed cells.