c-Rel is a proto-oncogene first identified as the cellular counterpart of the v-Rel oncogene derived from the avian reticuloendotheliosis retrovirus (REV-T). It was subsequently discovered that c-Rel belongs to the NF-kappaB/Rel transcription factor family whose members share a common DNA recognition motif and similar signaling pathways. Despite the similarities, however, each NF-kappaB/Rel member possesses unique properties with regard to tissue expression pattern, response to receptor signals and target gene specificity. These differences are fairly evident from the non-redundant phenotypes exhibited by individual NF-kappaB/Rel knockout mice. Hence the work described in this review will compare and contrast the various physiological functions of c-Rel to those of other NF-kappaB members, particularly with respect to the regulation of proliferation, survival and effector functions in multiple hematopoietic and immunological cell types. The study of c-Rel knockout mice in several disease models will also be discussed as they reveal an important role for c-Rel in response to allergens, auto-antigens, allo-antigens and pathogenic infection. BioEssays 25:767-780, 2003.
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