8 results on '"Rho guanosine triphosphatase"'
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2. Characterization of RhoBTB-dependent Cul3 ubiquitin ligase complexes — Evidence for an autoregulatory mechanism
- Author
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Berthold, Jessica, Schenková, Kristína, Ramos, Sonia, Miura, Yoshie, Furukawa, Manabu, Aspenström, Pontus, and Rivero, Francisco
- Subjects
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RHO GTPases , *UBIQUITIN , *TUMOR suppressor proteins , *PROTEIN-protein interactions , *MICROTUBULES , *GENES - Abstract
Abstract: RhoBTB proteins are atypical members of the Rho family of small GTPases. Two of the three RhoBTB proteins, RhoBTB1 and RhoBTB2, have been proposed as tumor suppressors and might function as adaptors of Cul3-dependent ubiquitin ligase complexes. Using yeast two-hybrid analysis and co-immunoprecipitation we show that all three RhoBTB proteins interact with Cul3. The interaction requires the N-terminal region of Cul3 and the first BTB domain of RhoBTB. RhoBTB3, the only RhoBTB with a prenylation motif, associates with vesicles that are frequently found in the vicinity of microtubules, suggesting a participation in some aspects of vesicle trafficking. We also show that RhoBTB2 and RhoBTB3 are capable of homo and heterodimerizing through the BTB domain region. The GTPase domain, which does not bind GTP, is able to interact with the BTB domain region, thus preventing proteasomal degradation of RhoBTB. This fits into a model in which an intramolecular interaction maintains RhoBTB in an inactive state, preventing the formation or the functionality of Cul3-dependent complexes. We also report a significantly decreased expression of RHOBTB and CUL3 genes in kidney and breast tumor samples and a very good correlation in the expression changes between RHOBTB and CUL3 that suggests that these genes are subject to a common inactivation mechanism in tumors. [Copyright &y& Elsevier]
- Published
- 2008
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3. Rho GTPases of the RhoBTB subfamily and tumorigenesis.
- Author
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Berthold, Jessica, Schenková, Kristína, and Rivero, Francisco
- Subjects
RHO GTPases ,GUANOSINE triphosphatase ,CARCINOGENESIS ,GTPASE-activating protein ,G proteins ,CELL cycle - Abstract
RhoBTB proteins constitute a subfamily of atypical members within the Rho family of small guanosine triphosphatases (GTPases). Their most salient feature is their domain architecture: a GTPase domain (in most cases, non-functional) is followed by a proline-rich region, a tandem of 2 broad-complex, tramtrack, bric à brac (BTB) domains, and a conserved C-terminal region. In humans, the RhoBTB subfamily consists of 3 isoforms: RhoBTB1, RhoBTB2, and RhoBTB3. Orthologs are present in several other eukaryotes, such as Drosophila and Dictyostelium, but have been lost in plants and fungi. Interest in RhoBTB arose when RHOBTB2 was identified as the gene homozygously deleted in breast cancer samples and was proposed as a candidate tumor suppressor gene, a property that has been extended to RHOBTB1. The functions of RhoBTB proteins have not been defined yet, but may be related to the roles of BTB domains in the recruitment of cullin3, a component of a family of ubiquitin ligases. A model emerges in which RhoBTB proteins are required to maintain constant levels of putative substrates involved in cell cycle regulation or vesicle transport through targeting for degradation in the 26S proteasome. RhoBTB proteins are engrossing the list of Rho GTPases involved in tumorigenesis. Unlike typical Rho GTPases (usually overexpressed or hyperactive), RhoBTB proteins appear to play a part in the carcinogenic process through a mechanism that involves the decreased or abolished expression of the corresponding genes, or more rarely, mutations that result in impaired functioning of the protein, presumably leading to the accumulation of RhoBTB substrates and alterations of the cellular homeostasis. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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- View/download PDF
4. Characterization of RhoBTB-dependent Cul3 ubiquitin ligase complexes. Evidence for an autoregulatory mechanism
- Author
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Kristína Schenková, Francisco Rivero, Manabu Furukawa, Yoshie Miura, Jessica Berthold, Pontus Aspenström, Sonia Ramos, German Research Foundation, Fundación Ramón Areces, University of Cologne, Swedish Research Council, National Cancer Institute (US), and National Institutes of Health (US)
- Subjects
rho GTP-Binding Proteins ,Proteasome Endopeptidase Complex ,Ubiquitin-Protein Ligases ,Rho guanosine triphosphatase ,GTPase ,Biology ,Models, Biological ,Article ,Cancer profiling array ,Cullin ,Mice ,Prenylation ,Ubiquitin ,Chlorocebus aethiops ,Tumor Cells, Cultured ,Animals ,Homeostasis ,Humans ,BTB domain ,RhoBTB ,Microscopy, Confocal ,Cullin Proteins ,Cell Biology ,Ubiquitin ligase ,Cell biology ,COS Cells ,biology.protein ,HeLa Cells - Abstract
S. R. was a recipient of a fellowship from Fundación Ramón Areces. F.R was supported by grants of the Center for Molecular Medicine Cologne (CMMC) and the Deutsche Forschungsgemeinschaft. Support by the Köln Fortune program of the Medical Faculty, University of Cologne to F.R. is also acknowledged. P.A. was supported by funds from the Ludwig Institute for Cancer Research, the Swedish Research Council and the Swedish Science Foundation. M. F. was supported by RR018759 from the National Center for Research Resources, a component of the National Institutes of Health and CA036727 from National Cancer Institute.
- Published
- 2008
5. Characterization of RhoBTB-dependent Cul3 ubiquitin ligase complexes. Evidence for an autoregulatory mechanism
- Author
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German Research Foundation, Fundación Ramón Areces, University of Cologne, Swedish Research Council, National Cancer Institute (US), National Institutes of Health (US), Berthold, Jessica, Schenkova, Kristína, Ramos, Sonia, Miura, Yoshie, Furukawa, Manabu, Aspenstrom, Pontus, Rivero, Francisco, German Research Foundation, Fundación Ramón Areces, University of Cologne, Swedish Research Council, National Cancer Institute (US), National Institutes of Health (US), Berthold, Jessica, Schenkova, Kristína, Ramos, Sonia, Miura, Yoshie, Furukawa, Manabu, Aspenstrom, Pontus, and Rivero, Francisco
- Published
- 2008
6. Genomic organization and expression profile of the small GTPases of the RhoBTB family in human and mouse
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Baggavalli P. Somesh, Francisco Rivero, Farshad Khademi, Sonia Ramos, Fundación Ramón Areces, German Research Foundation, and University of Cologne
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Male ,rho GTP-Binding Proteins ,Subfamily ,Rho guanosine triphosphatase ,GTPase ,Biology ,Signal transduction ,medicine.disease_cause ,Cell Line ,Mice ,Gene duplication ,Genetics ,medicine ,Tumor Cells, Cultured ,Animals ,Humans ,Expression pattern ,Amino Acid Sequence ,BTB domain ,RhoBTB ,Gene ,Phylogeny ,Cytoskeleton ,Genomic organization ,Cancer ,Binding Sites ,Base Sequence ,Sequence Homology, Amino Acid ,Fugu ,Gene Expression Profiling ,General Medicine ,Exons ,Introns ,Isoenzymes ,Genes ,Female ,Carcinogenesis ,HeLa Cells - Abstract
Members of the RhoBTB subfamily of Rho GTPases are present in vertebrates, Drosophila and Dictyostelium. RhoBTB proteins are characterized by a modular organization, consisting of a GTPase (guanosine triphosphatase) domain, a proline rich region, a tandem of two BTB (road-Complex, ramtrack, and ric à brac) domains and a C-terminal region of unknown function and might act as docking points for multiple components participating in signal transduction cascades. We have determined the genomic organization and the expression pattern of the three RHOBTB genes of human and mouse. The exon–intron organization of each gene is conserved in three vertebrate species (human, mouse and Fugu). RHOBTB1 and RHOBTB2 have a similar exon–intron organization and are closely related to the single gene encoding the RhoBTB orthologs of two insect species. By contrast, the exon–intron organization of RHOBTB3 differed substantially from that of the two other genes, indicating that this gene arose by a duplication event independent of the one that gave rise to RHOBTB1 and RHOBTB2. RHOBTB1 (located on chromosome 10) and RHOBTB3 (located on chromosome 5) appear ubiquitously expressed. However, they display a differential pattern of expression: RHOBTB1 showed high levels in stomach, skeletal muscle, placenta, kidney and testis, whereas RHOBTB3 was highly expressed in neural and cardiac tissues, pancreas, placenta and testis. RHOBTB2 (located on chromosome 8) showed much lower levels of expression than the other two human RHOBTB genes and it was most abundant in neural tissues. The expression patterns of the human and mouse genes were roughly comparable. All three genes were also detected in fetal tissues, and in a number of cell lines RHOBTB3 predominates. RHOBTB genes are upregulated in some cancer cell lines, suggesting that these proteins might participate in tumorigenesis., S.R. is the recipient of a fellowship from Fundación Ramón Areces and F.K. is the recipient of a fellowship from the Köln Fortune Program. This work was supported by the Deutsche Forschungsgemeinschaft (RI 1034/2) and by the Köln Fortune Program (Faculty of Medicine, University of Cologne).
- Published
- 2002
7. Genomic organization and expression profile of the small GTPases of the RhoBTB family in human and mouse
- Author
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Fundación Ramón Areces, German Research Foundation, University of Cologne, Ramos, Sonia, Kadhemi, Farshad, Somesh, Baggavalli P., Rivero, Francisco, Fundación Ramón Areces, German Research Foundation, University of Cologne, Ramos, Sonia, Kadhemi, Farshad, Somesh, Baggavalli P., and Rivero, Francisco
- Abstract
Members of the RhoBTB subfamily of Rho GTPases are present in vertebrates, Drosophila and Dictyostelium. RhoBTB proteins are characterized by a modular organization, consisting of a GTPase (guanosine triphosphatase) domain, a proline rich region, a tandem of two BTB (road-Complex, ramtrack, and ric à brac) domains and a C-terminal region of unknown function and might act as docking points for multiple components participating in signal transduction cascades. We have determined the genomic organization and the expression pattern of the three RHOBTB genes of human and mouse. The exon–intron organization of each gene is conserved in three vertebrate species (human, mouse and Fugu). RHOBTB1 and RHOBTB2 have a similar exon–intron organization and are closely related to the single gene encoding the RhoBTB orthologs of two insect species. By contrast, the exon–intron organization of RHOBTB3 differed substantially from that of the two other genes, indicating that this gene arose by a duplication event independent of the one that gave rise to RHOBTB1 and RHOBTB2. RHOBTB1 (located on chromosome 10) and RHOBTB3 (located on chromosome 5) appear ubiquitously expressed. However, they display a differential pattern of expression: RHOBTB1 showed high levels in stomach, skeletal muscle, placenta, kidney and testis, whereas RHOBTB3 was highly expressed in neural and cardiac tissues, pancreas, placenta and testis. RHOBTB2 (located on chromosome 8) showed much lower levels of expression than the other two human RHOBTB genes and it was most abundant in neural tissues. The expression patterns of the human and mouse genes were roughly comparable. All three genes were also detected in fetal tissues, and in a number of cell lines RHOBTB3 predominates. RHOBTB genes are upregulated in some cancer cell lines, suggesting that these proteins might participate in tumorigenesis.
- Published
- 2002
8. Differential properties of D4/LyGDI versus RhoGDI: phosphorylation and rho GTPase selectivity
- Author
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Philippe Chavrier, Toshifumi Azuma, Jean-Pierre Gorvel, Joëlle Boretto, and Tsu-Chung Chang
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RHOA ,Rho guanosine triphosphatase ,Molecular Sequence Data ,Biophysics ,Guanosine ,RAC1 ,CDC42 ,GTPase ,Biochemistry ,Antibodies ,Substrate Specificity ,chemistry.chemical_compound ,Cytosol ,GTP-binding protein regulators ,rho Guanine Nucleotide Dissociation Inhibitor beta ,Antibody Specificity ,GTP-Binding Proteins ,Structural Biology ,Tumor Cells, Cultured ,Genetics ,Humans ,rho-Specific Guanine Nucleotide Dissociation Inhibitors ,Amino Acid Sequence ,Phosphorylation ,Molecular Biology ,Guanine Nucleotide Dissociation Inhibitors ,rho Guanine Nucleotide Dissociation Inhibitor alpha ,Guanosine diphosphate dissociation inhibitor ,biology ,Tumor Suppressor Proteins ,GTPase-Activating Proteins ,Proteins ,Hematopoietic cell ,Cell Biology ,Peptide Fragments ,Guanosine nucleotide dissociation inhibitors ,Cell biology ,Kinetics ,chemistry ,Guanosine diphosphate ,biology.protein ,Tetradecanoylphorbol Acetate - Abstract
RhoA/B/C and CDC42/Rac, which form two subgroups of the rho guanosine triphosphatase (GTPase) family, regulate various aspects of actin cytoskeleton organisation. In cytosol, guanosine diphosphate (GDP) dissociation inhibitor (GDI) interacts with and maintains rho GTPases in their inactive GDP-bound form. RhoGDI is a ubiquitously expressed GDI, whereas D4/LyGDI is hematopoietic cell-specific and 10-fold less potent than RhoGDI in binding to and regulating rho GTPases. We have combined microanalytical liquid chromatography with the use of specific antibodies in order to separate D4/LyGDI and RhoDGI-complexes from the cytosol of U937 cells and to demonstrate that the two GDIs associate with different rho protein partners. RhoGDI can form a complex with CDC42Hs, RhoA, Rac1 and Rac2, while none of these GTPases was found to interact with D4/LyGDI. In addition, we found that stimulation of U937 cells with phorbol ester leads to phosphorylation of D4/LyGDI. Our results suggest that LyGDI forms complexes with specific rho GTPases expressed in hematopoietic cells where it may regulate specific pathways.
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