THE RELOCALIZATION OF V-REL FROM THE NUCLEUS TO THE CYTOPLASM COINCIDES WITH INDUCTION OF EXPRESSION OF IKBA AND NFKB1 AND STABILIZATION OFI-KAPPA-B-ALPHA

The v-Rel oncogene induces the expression of major histocompatibility complex class I and II proteins and the interleukin-2 receptor more ef ficiently than does c-Rel (R. Hrdlickova, J. Nehyba, and E. H. Humphri es, J. Virol. 68:308-319, 1994). The kinetics with which these immunor egulatory receptors are induced in B- and T-lymphoid cell lines and ch icken embryo fibroblast cultures expressing c-Rel or v-Rel have been e xamined. v-Rel induced the expression of major histocompatibility comp lex classes I and II and interleukin-2 receptor more efficiently than did c-Rel at later times after infection. In all three cell types, thi s 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 I kappa B-alpha. Coinfection by retroviral vectors expressin g v-Rel, I kappa B-alpha, or NF-kappa B1 demonstrated that either I ka ppa B-alpha Or NF-kappa B1 can contribute to the shift of v-Rel to the cytoplasmic compartment. The induction of nfkb1 and Ikba mRNA and the stabilization of I kappa B-alpha by v-Rel were shown to be responsibl e for these effects. In comparison with c-Rel, the expression of v-Rel was associated with lower levels of transcription of these genes. How ever, the ability of v-Rel to stabilize I kappa B-alpha remained uncha nged. The ability of v-Rel to stabilize I kappa B-alpha but poorly ind uce Ikba mRNA expression relative to c-Rel may play a role in regulati ng gene expression, thereby leading to transformation.