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You, M, Ku, PT, Hrdlicková, R and Bose, HR Jr (1997) ch-IAP1, a member of the inhibitor-of-apoptosis protein family, is a mediator of the antiapoptotic activity of the v-Rel oncoprotein. Mol. Cell. Biol. 17:7328-41
The oncoprotein v-Rel, a member of the Rel/NF-kappaB family of transcription factors, induces neoplasias and inhibits apoptosis. To identify differentially regulated cellular genes and to evaluate their relevance to transformation and apoptosis in v-Rel-transformed cells, mRNA differential display has been used. One of the recovered cDNAs corresponds to a gene that was highly expressed in v-Rel-transformed fibroblasts. Analysis of the isolated full-length cDNA of a chicken inhibitor-of-apoptosis protein (ch-IAP1) revealed that it encodes a 68-kDa protein that is highly homologous to members of the IAP family, such as human c-LAP1. 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 of 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 lines transformed by several other unrelated tumor 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 transformed spleen cells inhibited apoptosis of these cells at the nonpermissive 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.
Amino Acid Sequence; Animals; Apoptosis/genetics; Apoptosis/physiology; Base Sequence; Caspase 1; Cell Line, Transformed; Chickens; Cysteine Endopeptidases/genetics; Cysteine Endopeptidases/physiology; DNA Primers/genetics; DNA, Complementary/genetics; Gene Expression; Humans; Inhibitor of Apoptosis Proteins; Molecular Sequence Data; Oncogene Proteins v-rel; Polymerase Chain Reaction; Proteins/genetics; Proteins/physiology; RNA, Messenger/genetics; Retroviridae Proteins, Oncogenic/genetics; Retroviridae Proteins, Oncogenic/physiology; Sequence Homology, Amino Acid; Temperature; Tissue Distribution