The relocalization of v-Rel from the nucleus to the cytoplasm coincides with induction of expression of Ikba and nfkb1 and stabilization of I kappa B-alpha

Abstract

The v-Rel oncogene induces the expression of major histocompatibility complex class I and II proteins and the interleukin-2 receptor more efficiently than does c-Rel (R. Hrdličková, J. Nehyba, and E. H. Humphries, J. Virol. 68:308-319, 1994). The kinetics with which these immunoregulatory receptors are induced in B-and T-lymphoid cell lines and chicken embryo fibroblast cultures expressing c-Rel or v-Rel have been examined. v-Rel induced the expression of major histocompatibility complex classes I and II and interleukin-2 receptor more efficiently than did c-Rel at later times after infection. In all three cell types, this increased efficiency was accompanied by a shift in the majority of v-Rel from the nucleus to the cytoplasm. The concomitant relocalization of v-Rel was also demonstrated during the in vitro transformation of spleen cells. The translocation coincided with increased steady-state levels of IB-␣. Coinfection by retroviral vectors expressing v-Rel, IB-␣, or NF-B1 demonstrated that either IB-␣ or NF-B1 can contribute to the shift of v-Rel to the cytoplasmic compartment. The induction of nfkb1and Ikba mRNA and the stabilization of IB-␣ by v-Rel were shown to be responsible for these effects. In comparison with c-Rel, the expression of v-Rel was associated with lower levels of transcription of these genes. However, the ability of v-Rel to stabilize IB-␣ remained unchanged. The ability of v-Rel to stabilize IB-␣ but poorly induce Ikba mRNA expression relative to c-Rel may play a role in regulating gene expression, thereby leading to transformation.

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

“…VOL. 69,1995 v-Rel-DEPENDENT ALTERATION OF B DNA BINDING 3371 B-cell line supports v-Rel expression and exhibits changes which correlate with Rel transformation (33)(34)(35)56). To provide additional evidence that the DNA-binding complexes in REV-T-transformed cells correspond to those in DT95 cells, a direct comparison of the complexes recognized by various anti-Rel sera was performed ( Fig.…”

“…4B). The relocalization of Rel is likely to be mediated by an increase in the levels of NF-B1, NF-B2, and IB-␣ in cells transformed by oncogenic Rel proteins (35,42). Twelve days after infection, new B DNA-binding com-plexes were detected in the nucleus of REV-TW-infected cells.…”

“…This definition of c-Rel functional domains is based primarily on studies of c-Rel (7,15,30,37,38,45,54,55,57), but some data obtained from the analysis of other Rel/NF-B proteins were taken into account (12,49). Mutations by which v-Rel differs from both turkey and chicken c-Rel (15,32,72) (35,42). The proliferation rate of v-Rel-expressing cells increases 10-fold at approximately the same time as the endogenous nuclear B DNA-binding complexes can be detected (34).…”

“…Temporally correlated with the relocalization of v-Rel to the cytoplasm, new B DNA-binding complexes can be detected in the nucleus. This is also the time at which NF-B1, NF-B2, and IB-␣ transcription becomes elevated in v-Rel-transformed cells (35,42). These new complexes contain v-Rel heterodimerized with c-Rel and other Rel/NF-B family members.…”

“…Several Rel/NF-B-regulated genes have been shown to be upregulated as a consequence of v-Rel expression. These include the high-mobility-group protein 14b, the major histocompatibility complex (MHC) genes class I and II, the interleukin-2 receptor (IL-2R), nfkb1, and Ikba (9,34,35,42). Two non-mutually-exclusive mechanisms, which are associated with transformation by v-Rel, have been proposed to explain the alterations in Rel/NF-B-controlled gene expression (23,29).…”