Search results for "RHOB"
showing 8 items of 18 documents
The ras-related small GTP-binding protein RhoB is immediate-early inducible by DNA damaging treatments.
1995
The low molecular weight GTP-binding proteins RhoA, RhoB, and RhoC are characterized as specific substrates for the ADP-ribosyltransferase C3 from Clostridium botulinum and are supposed to be involved in the organization of the microfilamental network and transformation. rhoB is known to be immediate-early inducible by growth factors and protein-tyrosine kinases. Since increasing evidence indicates overlapping of growth factor- and UV-induced signal pathways, we studied the effect of UV light and other genotoxic agents on early rhoB transcription. Within 30 min after UV irradiation of NIH3T3 cells, the amount of rhoB mRNA increased 3-4-fold. Elevated rhoB mRNA was accompanied by an increase…
Transcriptional activation of the small GTPase gene rhoB by genotoxic stress is regulated via a CCAAT element
2001
The gene encoding the Ras-related GTPase RhoB-specific is immediate-early inducible by genotoxic treatments. Regulation of transcriptional activation of rhoB is still unclear. Here we show that cells lacking either p53 or c-Fos are not different from wild-type cells with respect to the level of rhoB induction upon UV irradiation, indicating that these transcription factors are not crucial for stimulation of rhoB mRNA expression. Extracts from UV-irradiated and non-irradiated cells revealed similar DNA-binding activities to a 0.17 kb rhoB promoter fragment harboring the functional element(s) necessary for stimulation of rhoB by UV light. By means of immunoprecipitation we found that an ATF-2…
rhoB encoding a UV-inducible Ras-related small GTP-binding protein is regulated by GTPases of the Rho family and independent of JNK, ERK, and p38 MAP…
1998
The small GTPase RhoB is immediate-early inducible by DNA damaging treatments and thus part of the early response of eukaryotic cells to genotoxic stress. To investigate the regulation of this cellular response, we isolated the gene for rhoB from a mouse genomic library. Sequence analysis of the rhoB gene showed that its coding region does not contain introns. The promoter region of rhoB harbors regulatory elements such as TATA, CAAT, and Sp1 boxes but not consensus sequences for AP-1, Elk-1, or c-Jun/ATF-2. The rhoB promoter was activated by UV irradiation, but not by 12-O-tetradecanoylphorbol-13-acetate treatment. rhoB promoter deletion constructs revealed a fragment of 0.17 kilobases in …
Activation of NF-kappaB and IL-8 by yersinia enterocolitica invasin protein is conferred by engagement of rac1 and MAP kinase cascades.
2003
International audience; Yersinia enterocolitica triggers activation of the nuclear factor (NF)-kappaB and production of the proinflammatory chemokine interleukin (IL)-8 in intestinal epithelial cells. This activation is due to adhesion of the bacteria via their outer membrane protein invasin to the host cells. Using Clostridium difficile toxins that specifically inactivate small GTPases, and transfection of inhibitory proteins of the Rho-GTPases, we demonstrate that Rac1, but not Cdc42 or Rho, is required for activation of NF-kappaB by invasin. Invasin activated the mitogen activated protein kinases (MAPK) p38 and c-Jun N-terminal protein kinase (JNK) but not extracellular signal regulated …
Rho GTPases in human breast tumours: expression and mutation analyses and correlation with clinical parameters
2002
In the present study, we addressed the question of a putative relevance of Rho proteins in tumour progression by analysing their expression on protein and mRNA level in breast tumours. We show that the level of RhoA, RhoB, Rac1 and Cdc42 protein is largely enhanced in all tumour samples analysed (n=15) as compared to normal tissues originating from the same individual. The same is true for 32P-ADP-ribosylation of Rho proteins which is catalysed by Clostridium botulinum exoenzyme C3. Also the amount of Rho-GDI and ERK2 as well as the level of overall 32P-GTP binding acvitity was tumour-specific elevated, yet to a lower extent than Rho proteins. Although the amount of Rho proteins was enhance…
Rho GTPases are over-expressed in human tumors.
1999
Small GTPases of the Rho family are involved in the regulation of a variety of cellular processes, such as the organization of the microfilamental network, cell-cell contact and malignant transformation. To address the question of whether Rho proteins are involved in carcinogenesis in man, we compared their expression in tumors from colon, breast and lung with that of the corresponding normal tissue originating from the same patient. As shown by Rho-specific 32P-ADP-ribosylation, as well as Western-blot analysis, the amount of RhoA protein was largely increased in all 3 types of tumors tested. The most dramatic differences in the expression of Rho GTPases were observed in breast tissue. All…
Rho GTPases: Promising Cellular Targets for Novel Anticancer Drugs
2006
Ras-homologous (Rho) GTPases play a pivotal role in the regulation of numerous cellular functions associated with malignant transformation and metastasis. Rho GTPases are localized at membranes and become activated upon stimulation of cell surface receptors. In their GTP-bound (=active) state, Rho proteins bind to effector proteins, thereby triggering specific cellular responses. Members of the Rho family of small GTPases are key regulators of actin reorganization, cell motility, cell-cell and cell-extracellular matrix (ECM) adhesion as well as of cell cycle progression, gene expression and apoptosis. Each of these functions is of importance for the development and progression of cancer. Fu…
Lovastatin inhibits Rho-regulated expression of E-selectin by TNFalpha and attenuates tumor cell adhesion.
2003
E-selectin mediated cell-cell adhesion plays an important role in inflammatory processes and extravasation of tumor cells. Tumor necrosis factor-alpha (TNF-alpha) induces E-selectin gene and protein expression in primary human endothelial cells (HUVEC) and in an endothelial cell line (EA.hy-926). As shown by ELISA and FACS analyses, HMG-CoA reductase inhibitors (e.g., lovastatin) impair the TNF-alpha stimulated increase in E-selectin protein expression. Similar results were obtained for E-selectin mRNA expression and promoter activity, indicating that the effect of lovastatin is based on inhibition of gene expression. The effective inhibitory concentration of lovastatin was in a physiologic…