The mouse c-rel protein has an N-terminal regulatory domain and a C-terminal transcriptional transactivation domain.

Abstract

We have shown that the murine c-rel protein can act as a transcriptional transactivator in both yeast and mammalian cells. Fusion proteins generated by linking rel sequences to the DNA-binding domain of the yeast trascriptional activator GAL4 activate transcription from a reporter gene linked in cis to a GAL4 binding site. The full-length mouse c-rel protein (588 amino acids long) is a poor transactivator; however, the C-terminal portion of the protein between amino acid residues 403 to 568 is a potent transcriptional transactivator. Deletion of the N-terminal half of the c-rel protein augments its transactivation function. We propose that c-rel protein has an N-terminal regulatory domain and a C-terminal transactivation domain which together modulate its function as a transcriptional transactivator.The immediate cellular response to external stimulus culminates in the induction of a large set of nuclear genes. Some of these early response genes are proto-oncogenes, and their products have been shown to be involved in the transcription of other genes (1,9,13,17,32,33,41,42). The theme of oncogenes as transcriptional factors or cofactors has been well illustrated by the Fos-Jun paradigm (13). The two nuclear oncoproteins associate to form heterodimers which bind to their cognate DNA motif to promote transactivation (12, 50). More recently, the product of the protooncogene myb has also been shown to act as a transcriptional activator (42, 62). Interestingly, the BAS1 protein, which is required for activation of GCN4-independent (basal) HIS4 transcription in yeast, shares homology to the N-terminal region of myb protein (58). The c-rel gene is a member of the immediate-early response gene family and is induced by serum and phorbol ester (TPA) (9). Its viral homolog, the v-rel protein, has been shown to function as a transcriptional activator in certain cell types (20,25).v-rel is the resident transforming gene of reticuloendotheliosis virus strain T, a highly oncogenic avian retrovirus that induces a rapidly fatal lymphoma in young birds (18,57). Reticuloendotheliosis virus strain transforms only avian lymphoid cells, and despite high levels of expression in chicken embryo fibroblasts, no transformed phenotype is evident (10,23,54). The product of v-rel is a 59-kilodalton phosphoprotein that is located in the cytoplasm of transformed spleen cells and in the nucleus of the nontransformed fibroblasts (10,19,22,54). However, subcellular localization appears to be irrelevant, because both cytoplasmic and nuclear forms of the v-rel protein can induce cellular transformation (23, 25). The v-rel protein has been shown to associate with a number of cellular proteins, including a closely associated serine-threonine protein kinase in both untransformed chicken embryo fibroblasts and transformed spleen cells (15,53,60 whereas in mouse and human cells it is 7.5 and 10 kilobases, respectively (8)(9)(10)26). Although c-rel expression is seen in many cell types, high levels are observed only in lymphoid cells (6,8).The c-rel prot...

Differences in κB DNA-binding properties of v-Rel and c-Rel are the result of oncogenic mutations in three distinct functional regions of the Rel protein

“…All Rel/NF-kB proteins contain a Rel homology region (RHR), a 300 amino acid sequence which is responsible for dimerization and DNA binding. The N-terminal region of RelB and the C-termini of c-Rel, RelA and RelB contain transactivation domains (Bull et al, 1990;Dobrzanski et al, 1993;Kamens et al, 1990;Schmitz and Baeuerle, 1991).…”

Two distinct mechanisms contribute to the constitutive activation of RelB in lymphoid cells.

“…The transactivation function in vivo resides predominantly in the different Rel-type proteins, i.e. RelA, RelB and c-Rel, that contain prototypical transactivation domains in their C-terminal domains (Bull et al, 1990; Kamens et al, 1990;Schmitz and Baeuerle, 1991;Dobrzanski et al, 1993). The transcriptionally active complexes that have been identified in cells are usually heterodimers between either NF-KB1 or NF-KB2 and one of the Rel-type (RelA, RelB and c-Rel) proteins, although strongly transactivating RelA homodimers and RelA/cRel heterodimers have also been described (Schmitz and Baeuerle, 1991;Urban et al, 1991;Hansen et al, 1994).…”

An interaction between the DNA-binding domains of RelA(p65) and Sp1 mediates human immunodeficiency virus gene activation.

“…The ReIA(p65) and RelB subunits are most highly homologous to c-Rel (49,58,59,61) and contain transactivation domains in their carboxy termini (12,27,31,49,55,60,61,63). Two related cDNAs encoding the larger precursor proteins of the 50-kDa DNAbinding subunits of NF-KB, NF-KB1(p105) (10,22,34,44) and NF-KB2(plOO) (9,47,62), have been isolated.…”