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-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.
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Department of Microbiology and Institute for Cellular and Molecular Biology, The University of Texas at Austin, 78712-1095, USA.
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Hrdlicková
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Bose
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D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D020170:Caspase 1; D002461:Cell Line, Transformed; D002645:Chickens; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008969:Molecular Sequence Data; D020572:Oncogene Proteins v-rel; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D013696:Temperature; D014018:Tissue Distribution; D044767:Ubiquitin-Protein Ligases
D017931:DNA Primers; D018076:DNA, Complementary; D051034:Inhibitor of Apoptosis Proteins; D020572:Oncogene Proteins v-rel; D011506:Proteins; D012333:RNA, Messenger; D015682:Retroviridae Proteins, Oncogenic; C494833:BIRC2 protein, human; D044767:Ubiquitin-Protein Ligases; D003546:Cysteine Endopeptidases; D020170:Caspase 1