Identification of v-Rel oncogene-induced inhibitor of apoptosis by differential display.
The v-Rel oncoprotein is a member of the Rel/NF-kappaB family of transcription factors. v-Rel induces oncogenic transformation and inhibits apoptosis. To identify aberrantly expressed cellular genes in v-Rel transformed cells, gene expression patterns in normal and v-Rel transformed cells were compared by mRNA differential display. Northern blotting analysis with radiolabeled cDNAs from differential display confirmed the reproducible differential expression of 10 transcripts in v-Rel transformed cells. One of the identified genes, termed ch-IAP1, encodes a chicken homolog of the inhibitor-of-apoptosis protein (IAP) family. ch-IAP1 contains N-terminal baculovirus IAP repeats (BIR), the hallmark of IAPs, and has a C-terminal RING finger motif commonly present in the other IAPs. Like other IAPs, ch-IAP1 is expressed predominantly in the cytoplasm of cells. ch-IAP1 is highly expressed in v-Rel transformed fibroblasts, B- and T-cell lines, and spleen cell lines. In contrast, ch-IAP1 expression levels were low in chicken cell lines transformed by several other unrelated tumor viruses. Additionally, ch-IAP1 expression is downregulated in temperature-sensitive (ts) v-Rel transformed spleen cells at the nonpermissive temperature. Overexpression of the full-length ch-IAP1 suppresses mammalian cell apoptosis induced by the interleukin-1-converting enzyme (ICE), a member of the mammalian caspase family of cysteine proteases. Furthermore, expression of exogenous ch-IAP1 inhibits apoptosis of ts v-Rel transformed spleen cells at the nonpermissive temperature.
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Department of Microbiology and the Institute for Cellular and Molecular Biology, University of Texas at Austin, 78712-1095, USA.
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D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001358:Avian Sarcoma Viruses / Q000235:genetics; D002460:Cell Line; D002642:Chick Embryo; D003001:Cloning, Molecular / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D020572:Oncogene Proteins v-rel; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics* / Q000494:pharmacology; D013696:Temperature; D014162:Transfection / Q000235:genetics; D014170:Transformation, Genetic / Q000235:genetics
D009363:Neoplasm Proteins; D020572:Oncogene Proteins v-rel; D012333:RNA, Messenger; D015682:Retroviridae Proteins, Oncogenic