RhoA-GDP regulates RhoB protein stability. Potential involvement of RhoGDIalpha
| Autor: | T T Giang, Ho, Sofia D, Merajver, Charles M, Lapière, Betty V, Nusgens, Christophe F, Deroanne |
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| Rok vydání: | 2008 |
| Předmět: |
rho GTP-Binding Proteins
Reverse Transcriptase Polymerase Chain Reaction Genetic Vectors Transfection Guanosine Diphosphate Models Biological Up-Regulation Protein Transport rhoC GTP-Binding Protein Animals Humans rho-Specific Guanine Nucleotide Dissociation Inhibitors Gene Silencing rhoA GTP-Binding Protein rhoB GTP-Binding Protein Guanine Nucleotide Dissociation Inhibitors Signal Transduction |
| Zdroj: | The Journal of biological chemistry. 283(31) |
| ISSN: | 0021-9258 |
| Popis: | RhoA plays a significant role in actin stress fibers formation. However, silencing RhoA alone or RhoA and RhoC did not completely suppress the stress fibers suggesting a residual "Rho-like" activity. RhoB, the third member of the Rho subclass, is a shortlived protein barely detectable in basal conditions. In various cell types, the silencing of RhoA induced a strong up-regulation of both total and active RhoB protein levels that were rescued by re-expressing RhoA and related to an enhanced half-life of the protein. The RhoA-dependent regulation of RhoB does not depend on the activity of RhoA but is mediated by its GDP-bound form. The stabilization of RhoB was not dependent on isoprenoid biosynthesis, Rho kinase, extracellular signal-regulated kinase, p38 mitogen-activated kinase, or phosphatidylinositol 3'-OH kinase pathways but required RhoGDIalpha. The forced expression of RhoGDIalpha increased RhoB half-life, whereas its knock-down antagonized the induction of RhoB following RhoA silencing. Moreover, a RhoA mutant (RhoAR68E) unable to bind RhoGDIalpha was significantly less efficient as compared with wild-type RhoA in reversing RhoB up-regulation upon RhoA silencing. These results suggest that, in basal conditions, RhoGDIalpha is rate-limiting and the suppression of RhoA makes it available to stabilize RhoB. Our results highlight RhoGDIalpha-dependent cross-talks that regulate the stability of RhoGTPases. |
| Databáze: | OpenAIRE |
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