| http://purl.uniprot.org/citations/15728253 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15728253 | http://www.w3.org/2000/01/rdf-schema#comment | "The small GTPases of the Rho family are key intermediates in cellular signalling triggered by activated cell-adhesion receptors. In this study, we took advantage of RNA interference (RNAi) using small interfering RNAs (siRNAs) to define the roles of the best-characterized members of the RhoGTPase family, RhoA, Rac1 and Cdc42, in the control of MMP-1, MMP-2 and type-I-collagen expression in normal human skin fibroblasts (HSFs). A specific and long-lasting repression, up to 7 days after transfection, of the three GTPases was achieved by transient transfection of specific siRNA. The silencing of Cdc42, but not that of RhoA or Rac1, induced a 15-fold increase in MMP-1 secretion. This upregulation was confirmed at the mRNA level and observed with two different siRNAs targeting Cdc42. Such a regulation was also observed in various human cell lines and was rescued by re-expressing wild-type Cdc42 encoded by a construct bearing silent mutations impeding its recognition by the siRNA. By contrast, MMP-2 and type-I-collagen expression was not affected by the individual silencing of each Rho GTPase. Cytokine protein array, enzyme-linked immunosorbent assays and reverse-transcription PCR measurements revealed that ablation of Cdc42 induced an overexpression of interleukin 8 and MCP-1. Although these cytokines are known to induce the expression of MMP-1, we showed that they were not involved in the Cdc42-mediated upregulation of MMP-1. Silencing of Cdc42 also induced an increased phosphorylation of ERK1/2 and p38 MAP kinase. The use of chemical inhibitors on Cdc42-ablated cells revealed that the upregulation of MMP-1 is dependent on the ERK1/2 pathways, whereas the p38 MAP kinase pathway displayed an inhibitory role. Simultaneous knock-down of two or three Rho GTPases allowed us to demonstrate that the RhoA-ROCK pathway was not involved in this regulation but that the silencing of Rac1 reduced the effect of Cdc42 suppression. These data suggest that, in vivo, when cell/extracellular-matrix interactions via integrins induce cytoskeleton organization, MMP-1 expression is maintained at a low level by Cdc42 via a repression of the Rac1 and ERK1/2 pathways. Therefore, Cdc42 contributes to ECM homeostasis and connective tissue integrity."xsd:string |
| http://purl.uniprot.org/citations/15728253 | http://purl.org/dc/terms/identifier | "doi:10.1242/jcs.01707"xsd:string |
| http://purl.uniprot.org/citations/15728253 | http://purl.uniprot.org/core/author | "Lambert C.A."xsd:string |
| http://purl.uniprot.org/citations/15728253 | http://purl.uniprot.org/core/author | "Lapiere C.M."xsd:string |
| http://purl.uniprot.org/citations/15728253 | http://purl.uniprot.org/core/author | "Nusgens B.V."xsd:string |
| http://purl.uniprot.org/citations/15728253 | http://purl.uniprot.org/core/author | "Ho T.T."xsd:string |
| http://purl.uniprot.org/citations/15728253 | http://purl.uniprot.org/core/author | "Catroux P."xsd:string |
| http://purl.uniprot.org/citations/15728253 | http://purl.uniprot.org/core/author | "Deroanne C.F."xsd:string |
| http://purl.uniprot.org/citations/15728253 | http://purl.uniprot.org/core/author | "Hamelryckx D."xsd:string |
| http://purl.uniprot.org/citations/15728253 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/15728253 | http://purl.uniprot.org/core/name | "J Cell Sci"xsd:string |
| http://purl.uniprot.org/citations/15728253 | http://purl.uniprot.org/core/pages | "1173-1183"xsd:string |
| http://purl.uniprot.org/citations/15728253 | http://purl.uniprot.org/core/title | "Cdc42 downregulates MMP-1 expression by inhibiting the ERK1/2 pathway."xsd:string |
| http://purl.uniprot.org/citations/15728253 | http://purl.uniprot.org/core/volume | "118"xsd:string |
| http://purl.uniprot.org/citations/15728253 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/15728253 |
| http://purl.uniprot.org/citations/15728253 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/15728253 |
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| http://purl.uniprot.org/uniprot/#_B4DHN0-mappedCitation-15728253 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15728253 |
| http://purl.uniprot.org/uniprot/#_B7ZAY4-mappedCitation-15728253 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15728253 |