Serum-dependent transcriptional networks identify distinct functional roles for H-Ras and N-Ras during initial stages of the cell cycle

Table 1 Functional signatures of differentially expressed genes induced or suppressed in H- ras ^-/- and/or N- ras ^-/- fibroblasts after serum stimulation for 1 hour (G0/G1 transition)

GO ID	Functional category	Gene %	P-value	Relevant genotype	Significant loci
Up-regulated genes
GO:0006955	Immunity and defense	10.5%	0.000209	N-ras^-/-	Fas, Cxcl10, Il6, Irf1, Psmb9, Mx1, Mx2, Cxcl2, Tap1, Ifi202b
GO:0006915	Apoptosis	9.6%	0.000250	N-ras^-/-	Bax, Bid, Fas, Gadd45b, Perp, Tnfrsf11b, Phlda1, Tnfaip3, Trp53
GO:0003677	Transcription	4.3%	0.000400	N-ras^-/-	Rela, Stat1, Stat5a, Trp53
GO:0005515	MAPK signaling cascade	3.2%	0.000896	N-ras^-/-	Fas, Mapkapk2, Gadd45b, Dusp8, Trp53, Map3k8, Flnb
GO:0003924	GTPase activity	5.3%	0,002511	N-ras^-/-	Ehd1, Mx1, Mx2, Iigp2, Rhoj
GO:0008283	Cell proliferation	10.3%	0.006678	H-ras^-/-	Gnb1, Vegfa, Irs2
Down-regulated genes
GO:0007049	Cell cycle	16.7%	0.000109	N-ras^-/-	Ccnd2, Ccng2, Cdkn2a, Ppp1cc, Spin, Tsc2, Anapc4, Sash1
GO:0005515	Cell adhesion and cytoskeleton organization	6.3%	0.000244	N-ras^-/-	Nras, Pik3r2, Ppp1cc
GO:0004910	Insulin signaling pathway	10.4%	0,000720	N-ras^-/-	Nras, Pik3r2, Ppp1cc, Tsc2, Pck2

Specific functional categories assigned by GeneCodis software [66] to particular subsets of the induced or repressed genes included in the dendrograms in Figure 3a. The software tool was used to search for gene annotation co-occurrences in the Gene Ontology (GO) and KEGG pathways databases, assigning values of statistical significance in each case. Functional categories are listed according to increasing P-value of significance for each relevant genotype. Columns provide information on functional GO ID and denomination, percentage of total number of induced or repressed genes in Figure 3a, statistical significance (P-value) of the functional assignment made in each case, and a representative list of differentially expressed loci associated with each functional category.

ISSN: 1474-760X