Hrdlicková R, Nehyba J, Roy A, Humphries E H, Bose H R
Department of Microbiology, University of Texas at Austin 78712-1095.
J Virol. 1995 Jan;69(1):403-13. doi: 10.1128/JVI.69.1.403-413.1995.
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. Hrdlicková, 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 of 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. Coninfection by retroviral vectors expressing v-Rel, I kappa B-alpha, or NF-kappa B1 demonstrated that either I kappa B-alpha 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 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 I kappa B-alpha remained unchanged. The ability of v-Rel to stabilize I kappa B-alpha but poorly induce Ikba mRNA expression relative to c-Rel may play a role in regulating gene expression, thereby leading to transformation.
与c-Rel相比,v-Rel癌基因能更有效地诱导主要组织相容性复合体I类和II类蛋白以及白细胞介素-2受体的表达(R. Hrdlicková、J. Nehyba和E. H. Humphries,《病毒学杂志》68:308 - 319,1994年)。已检测了在表达c-Rel或v-Rel的B淋巴细胞系、T淋巴细胞系和鸡胚成纤维细胞培养物中诱导这些免疫调节受体的动力学。在感染后的较晚时间,v-Rel比c-Rel更有效地诱导了主要组织相容性复合体I类和II类以及白细胞介素-2受体的表达。在所有这三种细胞类型中,这种效率的提高伴随着大多数v-Rel从细胞质的细胞核中转移出来。在脾细胞的体外转化过程中也证实了v-Rel的伴随重新定位。这种易位与IκB-α的稳态水平增加相吻合。表达v-Rel、IκB-α或NF-κB1的逆转录病毒载体共感染表明,IκB-α都可促使v-Rel向细胞质区室转移。v-Rel对nfkb1和Ikba mRNA的诱导以及IκB-α的稳定被证明是造成这些效应的原因。与c-Rel相比,v-Rel的表达与这些基因的较低转录水平相关。然而,v-Rel稳定IκB-α的能力保持不变。相对于c-Rel,v-Rel稳定IκB-α但诱导Ikba mRNA表达能力较差可能在调节基因表达中起作用,从而导致细胞转化。