Genetic characterization of human c-rel sequences.

Abstract

We isolated and sequenced a human genomic-DNA segment that is homologous to a portion of v-rel, the transforming gene of reticuloendotheliosis virus (strain T). We also localized the human rel sequences to human chromosome 2 by screening a panel of rodent x human somatic-cell hybrids with the newly described human rel segment. Cellular homologs of retroviral transforming genes have been identified in birds and mammals, in which these homologs are thought to perform important roles in regulating cell proliferation and differentiation (for a review, see reference 2). Recent studies suggest, however, that specific alterations in normal cellular oncogene structure and expression may themselves initiate cellular transformation in the absence of retroviral infection (e.g., see references 7, 15, 24, and 30). Such observations have prompted investigators to clone cellular oncogene homologs to study their normal biological properties and to determine whether alterations in these properties are consistently associated with naturally occurring, nonvirally induced malignancies. In this study, we determined the nucleotide sequence and chromosomal localization of a cloned human DNA segment carrying two putative exons homologous to the transforming gene (v-rel) of reticuloendotheliosis virus strain T (REV-T). The human c-rel sequences may provide a useful tool for studying the structure and function of this cellular oncogene in mammals.REV-T is a replication-defective (11) type C retrovirus (3,12,25,36) that induces acute leukemia in young chickens and turkeys (32). It is the only known acutely transforming member (9, 10) of a retroviral family that includes spleen necrosis virus, chick syncytial virus, duck infectious anemia virus, and the REV-T helper reticuloendotheliosisassociated virus (REV-A) (11,14). The REV-T genome carries a genomic substitution of approximately 1.42 kilobases (kb) near its 3' end (4, 6, 29) that is required for cellular transformation (5). This sequence, termed v-rel, is believed to have been derived from several exons of a turkey cellular gene (4,27,35), and recent molecular analyses of the turkey c-rel locus support this hypothesis (33). We began our investigation by performing Southern transfer and hybridization experiments to determine whether v-rel homologies could also be detected in humans and other mammals. The results of one such experiment in which cellular DNAs of hamsters, mice, humans, and chickens were hybridized with Sst v-rel, a 514-base-pair (bp) subclone of v-rel, are shown in Fig. le. After a 3-day exposure, one or two rel-homologous DNA bands were noted in all of the lanes, including those containing human DNA (see also reference 4).We next used Sst v-rel to screen (1) a human partial HaeIII-AluI genomic-DNA library (18) This fragment (pPHHSrel-1) was subcloned for further sequence analysis. Additional Sst v-rel homologies could not be identified, leading us to speculate either that the phage clone carried only a small portion of the human c-rel gene or that HSrel-1 and Sst v-r...

Distinct mechanisms for regulation of the interleukin-8 gene involve synergism and cooperativity between C/EBP and NF-kappa B.

“…NF-KB and C/EBP are two important transcription factor families that are involved in immune and inflammatory functions as well as cell growth and differentiation. NF-KB is typically composed of a 50-kDa (10,16,23) and a 65-kDa (33,36) subunit that share with other members of this family, such as c-Rel (13,18) and NF-KB p52 (9,31,37), the highly homologous N terminus, the so-called Rel homology domain. NF-KB family members bind as a dimer to a relatively well-conserved sequence that is found in a variety of genes (4).…”

Detection of c-rel-related transcripts in mouse hematopoietic tissues, fractionated lymphocyte populations, and cell lines.

“…Recently, we presented evidence that unique c-rel loci could also be identified in humans, mice, and cats, all of which provide potentially useful genetic model systems for studying the function of this proto-oncogene (3,4). To date, however, no clear picture has emerged regarding c-rel transcription in any mammalian group, a problem based partly on the fact that the rel-specific probes used in previous studies were derived from the distantly related avian viral rel oncogene (19,23,25,28).…”

“…1A; 4) as a probe to screen total cellular RNA samples from several murine tissues (7,10,20). The human probe, pPHHSrel-1, carries two highly conserved c-rel exons (4) and hybridizes under moderately high stringency to a unique c-rel genetic locus on mouse chromosome 11 (3). The human probe detected a 7.5-kb RNA in thymus and spleen RNA preparations (Fig.…”

Transcriptional induction of the murine c-rel gene with serum and phorbol-12-myristate-13-acetate in fibroblasts.

“…The 32-microglobulin-specific probes were obtained by using plasmid pSPT672 (which contains P2-microglobulin cDNA) as a template for SP6 RNA polymerase cut with AccI (for the 180-nucleotide probe) or Hindlll (for the 250-nucleotide probe) (32). (29), blotted onto nitrocellulose, and hybridized with a nick-translated human c-rel probe (8). The specific activity of the probe was about 108 cpm/gig, and it was used at a concentration of 106 cpmlml.…”