Differential regulation of the inhibitor of apoptosis ch-IAP1 by v-rel and the proto-oncogene c-rel.
The v-rel oncogene encoded by reticuloendotheliosis virus is the acutely transforming member of the Rel/NF-kappaB family of transcription factors. v-Rel is a truncated and mutated form of c-Rel and transforms cells by inducing the aberrant expression of genes regulated by Rel/NF-kappaB proteins. The expression of ch-IAP1, a member of the inhibitor-of-apoptosis family, is highly elevated in cells expressing v-Rel and contributes to the immortalization of cells transformed by this oncoprotein. In this study we demonstrate that the elevated expression of ch-IAP1 in v-Rel-expressing cells is due to an increased rate of transcription. The ch-IAP1 promoter was isolated, and four Rel/NF-kappaB binding sites were identified upstream of the transcription start site. Two kappaB sites proximal to the transcription start site were required for v-Rel to activate the ch-IAP1 promoter. While c-Rel also utilized these sites, a third more-distal kappaB site was required for its full activation of the ch-IAP1 promoter. Differences in the transactivation domains of v-Rel and c-Rel are responsible for their different abilities to utilize these sites and account for their differential activation of the ch-IAP1 promoter. Although c-Rel was a more potent activator of the ch-IAP1 promoter than v-Rel in transient reporter assays, cells stably overexpressing c-Rel failed to maintain high levels of ch-IAP1 expression. The reduction of ch-IAP1 expression in these cells correlated with the efficient regulation of c-Rel by IkappaBalpha. The ability of v-Rel to escape IkappaBalpha regulation allows for the gradual and sustained elevation of ch-IAP1 expression directly contributing to the transforming properties of v-Rel.
Kralova
Jarmila
J
Section of Molecular Genetics and Microbiology and the Institute of Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas 78712-1095, USA.
Liss
Andrew S
AS
Bargmann
William
W
Pendleton
Cullen
C
Varadarajan
Janani
J
Ulug
Emin
E
Bose
Henry R
HR
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D018076:DNA, Complementary / Q000235:genetics; D005786:Gene Expression Regulation; D020573:Genes, rel; D020672:I-kappa B Proteins / Q000378:metabolism; D007700:Kinetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D000072000:NF-KappaB Inhibitor alpha; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D012313:RNA / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014170:Transformation, Genetic; D051636:X-Linked Inhibitor of Apoptosis Protein
D018076:DNA, Complementary; D020672:I-kappa B Proteins; D011506:Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; D000072000:NF-KappaB Inhibitor alpha; D012313:RNA