Human Gene Set: BERENJENO_TRANSFORMED_BY_RHOA_REVERSIBLY_DN

For the Mouse gene set with the same name, see BERENJENO_TRANSFORMED_BY_RHOA_REVERSIBLY_DN

Standard name BERENJENO_TRANSFORMED_BY_RHOA_REVERSIBLY_DN
Systematic name M3034
Brief description Genes down-regulated in NIH3T3 cells (fibroblasts) transformed by expression of contitutively active (Q63L) form of RHOA [GeneID=387] off plasmid vector; their expression reverted completely after treatment with Y27632 [PubChem=123862], an inhibitor of ROCK proteins.
Full description or abstract 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.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 17213802   Authors: Berenjeno IM,Núñez F,Bustelo XR
Exact source Table 3S: RhoAi < 1 & RhoA > 1
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Source species Mus musculus
Contributed by Leona Saunders (MSigDB Team)
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identifier namespace		 AFFY_MG_U74
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Version history 3.0: First introduced

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