Fritz G, Gnad R, Kaina B
Institute of Toxicology, University of Mainz, Germany.
Anticancer Res. 1999 May-Jun;19(3A):1681-8.
Ras-homologous (Rho) GTPases are involved in the regulation of a variety of cellular processes such as the organization of the actin cytoskeleton, malignant transformation and genotoxic stress-induced signaling. Here we show that, among the family of Rho GTPases, specifically rhoB mRNA expression is rapidly induced upon UV-irradiation, whereas the level of rac 1 and cdc42 mRNA is not affected. Increase in rhoB mRNA was accompanied by a approximately 4-fold increase in the amount of membrane-bound RhoB protein. Basal expression of rhoB mRNA appears to be cell-type specific with low amounts in rodent NIH 3T3, V79, H4IIE, CHO and human HaCat cells and comparably high amounts in monkey COS, human HeLa and HepG2 cells. In rabbit tissues, exceptionally high levels of rhoB mRNA and RhoB protein were found in lung whereas its expression was quite low in heart, liver, spleen and kidney. Variations in rhoB mRNA expression level are not due to cell-type specific differences in rhoB mRNA stability as shown by inhibitor experiments. However, transiently transfected rhoB promoter CAT construct was expressed at significantly higher level in HeLa and HepG2 as compared to NIH 3T3 and CHO cells. Thus, cell-type specific differences in the level of rhoB mRNA are likely to be due to variations in the transcriptional activity of the rhoB gene. The data indicate that, among the family of Rho GTPases, only the expression of rhoB is rapidly stimulated by genotoxic stress. Furthermore basal rhoB expression appears to be regulated in a cell and tissue-type specific manner. This may be related to yet unknown tissue-specific physiological function of RhoB.
Ras同源（Rho）GTP酶参与多种细胞过程的调控，如肌动蛋白细胞骨架的组织、恶性转化以及基因毒性应激诱导的信号传导。在此我们表明，在Rho GTP酶家族中，紫外线照射后，rhoB mRNA的表达会迅速被诱导，而rac 1和cdc42 mRNA的水平不受影响。rhoB mRNA的增加伴随着膜结合RhoB蛋白量约4倍的增加。rhoB mRNA的基础表达似乎具有细胞类型特异性，在啮齿动物NIH 3T3、V79、H4IIE、CHO细胞以及人类HaCat细胞中含量较低，而在猴COS、人类HeLa和HepG2细胞中含量相对较高。在兔组织中，肺中发现rhoB mRNA和RhoB蛋白水平异常高，而在心脏、肝脏、脾脏和肾脏中其表达相当低。如抑制剂实验所示，rhoB mRNA表达水平的变化并非由于rhoB mRNA稳定性的细胞类型特异性差异。然而，与NIH 3T3和CHO细胞相比，瞬时转染的rhoB启动子CAT构建体在HeLa和HepG2细胞中的表达水平显著更高。因此，rhoB mRNA水平的细胞类型特异性差异可能是由于rhoB基因转录活性的变化。数据表明，在Rho GTP酶家族中，只有rhoB的表达受到基因毒性应激的快速刺激。此外，rhoB的基础表达似乎以细胞和组织类型特异性的方式受到调控。这可能与RhoB尚未明确的组织特异性生理功能有关。
