STANDARD_NAME	BERENJENO_TRANSFORMED_BY_RHOA_REVERSIBLY_DN
SYSTEMATIC_NAME	M3034
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/BERENJENO_TRANSFORMED_BY_RHOA_REVERSIBLY_DN
NAMESPACE	AFFY_MG_U74
DESCRIPTION_BRIEF	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.
DESCRIPTION_FULL	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.
PMID	17213802
GEOID	GSE5913
AUTHORS	Berenjeno IM,Núñez F,Bustelo XR
CONTRIBUTOR	Leona Saunders
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 3S: RhoAi < 1 & RhoA > 1
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	100277_at,100381_at,101934_at,101993_at,102798_at,102907_at,103258_at,103362_at,103664_r_at,104407_at,104712_at,160261_i_at,160320_at,160469_at,92777_at,93102_f_at,93285_at,93294_at,93436_i_at,93541_at,93615_at,93974_at,94147_at,96343_at,96426_at,96775_at,97409_at,97498_at,98623_g_at,99057_at,99959_at
GENE_SYMBOLS	INHBA,ACTA1,FEZ2,TNC,ADM,PHLDB2,LY75,PTGER4,CINP,ALCAM,MYC,LATS2,SORBS1,THBS1,CCN1,ACTG2,DUSP6,CCN2,,TAGLN,PBX3,ERRFI1,SERPINE1,ACTN4,TMSB4X,CBX1,IRGM,FHL1,IGF2,THY1,AK4
FOUNDER_NAMES