Mutations in the DNA-binding and dimerization domains of v-Rel are responsible for altered kappa B DNA-binding complexes in transformed cells.

AUTOR(ES)

Hrdlicková, R

RESUMO

The c-rel proto-oncogene encodes a member of the Rel/NF-kappa B family of transcription factors. The oncogenic viral form, v-rel, transduced by avian reticuloendotheliosis virus T, induces lymphoid tumors. v-Rel transformation may be mediated directly by binding of v-Rel to cognate DNA sites, resulting in altered gene expression, and/or indirectly by releasing Rel/NF-kappa B transcription factors from cytoplasmic retention molecules, resulting in their translocation to the nucleus and the inappropriate expression of genes under kappa B control. v-Rel-transformed cell lines of different phenotypes contained v-Rel as well as endogenous kappa B DNA-binding proteins in nuclear extracts. Kinetic analysis with avian leukosis virus-transformed B-cell lines expressing v-Rel or c-Rel indicated that the presence of endogenous kappa B DNA-binding proteins in the nucleus is temporally correlated with the relocalization of v-Rel to the cytoplasm. Supershift analysis of these DNA-binding complexes revealed that v-Rel was present in all of the nuclear DNA-binding complexes heterodimerized with c-Rel, NF-kappa B1, and other proteins. In contrast, c-Rel-transformed cells exhibited a less-complex pattern of nuclear kappa B DNA-binding complexes, and the nuclear appearance of these endogenous complexes was not observed. Studies with c-/v-Rel hybrids suggest that the induction of the endogenous kappa B DNA-binding complexes is the result of the mutations in the C-terminal region of the Rel homology (RH) domain of v-Rel. Moreover, v-Rel differed from c-Rel in its DNA-binding specificity. The altered DNA-binding specificity of v-Rel was associated with mutations located in the N-terminal part of the RH domain of v-Rel. These results suggest that two different regions of v-Rel (both located in the RH domain) influence the formation of kappa B DNA-binding complexes differently.

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