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Transcriptomal profiling of the cellular transformation induced by Rho subfamily GTPases

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dc.creator Berenjeno, Inmaculada M.
dc.creator Núñez, Fátima
dc.creator Bustelo, Xosé R.
dc.date 2008-06-17T09:22:51Z
dc.date 2008-06-17T09:22:51Z
dc.date 2007-06
dc.date.accessioned 2017-01-31T01:42:16Z
dc.date.available 2017-01-31T01:42:16Z
dc.identifier Oncogene 26(29): 4295–4305 (2007)
dc.identifier 0950-9232
dc.identifier http://hdl.handle.net/10261/5127
dc.identifier 10.1038/sj.onc.1210194
dc.identifier.uri http://dspace.mediu.edu.my:8181/xmlui/handle/10261/5127
dc.description El pdf del artículo es el manuscrito de autor.
dc.description We have used microarray technology to identify the transcriptional targets of Rho subfamily guanosine 5′-triphosphate (GTP)ases in NIH3T3 cells. This analysis indicated that murine fibroblasts transformed by these proteins show similar transcriptomal profiles. Functional annotation of the regulated genes indicate that Rho subfamily GTPases target a wide spectrum of functions, although loci encoding proteins linked to proliferation and DNA synthesis/transcription are upregulated preferentially. Rho proteins promote four main networks of interacting proteins nucleated around E2F, c-Jun, c-Myc and p53. Of those, E2F, c-Jun and c-Myc are essential for the maintenance of cell transformation. Inhibition of Rock, one of the main Rho GTPase targets, leads to small changes in the transcriptome of Rho-transformed cells. Rock inhibition decreases c-myc gene expression without affecting the E2F and c-Jun pathways. Loss-of-function studies demonstrate that c-Myc is important for the blockage of cell-contact inhibition rather than for promoting the proliferation of Rho-transformed cells. However, c-Myc overexpression does not bypass the inhibition of cell transformation induced by Rock blockage, indicating that c-Myc is essential, but not sufficient, for Rock-dependent transformation. These results reveal the complexity of the genetic program orchestrated by the Rho subfamily and pinpoint protein networks that mediate different aspects of the malignant phenotype of Rho-transformed cells. Keywords: Rho/Rac GT
dc.description This work was supported by grants from the Ramón Areces Foundation, the NCI/NIH (5RO1-CA73735-10) and the Spanish Ministry of Education and Science Special Action on Genomics and Proteomics (GEN2003-20239-C06-01). IMB was supported by a Spanish Ministry of Education and Science FPU fellowship (FP2000-6489). FN was partially supported by a Ernst Schering Foundation fellowship. The genomic data of this work are deposited in the NCBI Gene Expression Omnibus database (Accession number: GSE5913).
dc.description Peer reviewed
dc.format 22195 bytes
dc.format application/pdf
dc.language eng
dc.publisher Nature Publishing Group
dc.relation http://dx.doi.org/10.1038/sj.onc.1210194
dc.rights openAccess
dc.subject Rho/Rac GTPases
dc.subject Microarray
dc.subject Proliferation
dc.subject Gene expression
dc.subject Transcription
dc.subject Rock
dc.subject c-Myc
dc.title Transcriptomal profiling of the cellular transformation induced by Rho subfamily GTPases
dc.type Artículo

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