Human Gene Set: OXFORD_RALA_AND_RALB_TARGETS_DN


Standard name OXFORD_RALA_AND_RALB_TARGETS_DN
Systematic name M1234
Brief description Genes down-regulated in the UMUC-3 cells (bladder cancer) after knockdown of both RALA and RALB [GeneID=5898;5899] by RNAi.
Full description or abstract Although the monomeric GTPases RalA and RalB have been shown to regulate a variety of transcription factors, little is known regarding the differences or similarities in transcriptional programs regulated by RalA compared to RalB. Further, the association of these transcriptional pathways to human carcinogenesis and progression remains unclear. Here, we studied the role of RalA and/or RalB in transcriptional regulation by combining short interfering RNA depletion of Ral with gene expression profiling via microarray in the human bladder cancer cell line, UMUC-3. A large number of genes were found to be similarly modulated in cells with RalA and RalB depletion, suggesting that RalA and RalB impinge on overlapping transcriptional signaling pathways. However, smaller sets of genes were modulated by depletion of RalA or RalB, indicating that these closely related proteins also regulate nonoverlapping transcriptional pathways. Computational analysis of upstream sequences of genes modulated by Ral depletion identified Ras-responsive element-binding protein (RREB)-1, as a putative Ral transcriptional target, which we verified experimentally. Importantly, as a group, Ral-regulated probe sets identified here were disproportionally represented among those differentially expressed as a function of human bladder transformation. Taken together, these data strongly suggest that Ral family members mediate both common and specific transcriptional programs that are associated with human cancer and identify RREB-1 as a novel transcriptional effector of Ral.
Collection ARCHIVED: Archived Founder gene sets that are referenced by current Hallmarks
      C2_NONE: ARCHIVED Curated
            C2_CGP: ARCHIVED Chemical and Genetic Perturbations
Source publication Pubmed 17496927   Authors: Oxford G,Smith SC,Hampton G,Theodorescu D
Exact source Table 1
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Source species Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
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Version history 3.1: First introduced

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