STANDARD_NAME	TIAN_TNF_SIGNALING_NOT_VIA_NFKB
SYSTEMATIC_NAME	M14666
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/TIAN_TNF_SIGNALING_NOT_VIA_NFKB
NAMESPACE	HUMAN_SEQ_ACCESSION
DESCRIPTION_BRIEF	Genes modulated in HeLa cells (cervical carcinoma) by TNF [GeneID=7124] not via NFKB pathway.
DESCRIPTION_FULL	Tumor necrosis factor (TNF) is a pro-inflammatory cytokine that controls expression of inflammatory genetic networks. Although the nuclear factor-kappaB (NF-kappaB) pathway is crucial for mediating cellular TNF responses, the complete spectrum of NF-kappaB-dependent genes is unknown. In this study, we used a tetracycline-regulated cell line expressing an NF-kappaB inhibitor to systematically identify NF-kappaB-dependent genes. A microarray data set generated from a time course of TNF stimulation in the presence or absence of NF-kappaB signaling was analyzed. We identified 50 unique genes that were regulated by TNF (Pr(F)<0.001) and demonstrated a change in signal intensity of+/-3-fold relative to control. Of these, 28 were NF-kappaB-dependent, encoding proteins involved in diverse cellular activities. Quantitative real-time PCR assays of eight characterized NF-kappaB-dependent genes and five genes not previously known to be NF-kappaB-dependent (Gro-beta and-gamma, IkappaBepsilon, interleukin (IL)-7R, and Naf-1) were used to determine whether they were directly or indirectly NF-kappaB regulated. Expression of constitutively active enhanced green fluorescent.NF-kappaB/Rel A fusion protein transactivated all but IL-6 and IL-7R in the absence of TNF stimulation. Moreover, TNF strongly induced all 12 genes in the absence of new protein synthesis. High probability NF-kappaB sites in novel genes were predicted by binding site analysis and confirmed by electrophoretic mobility shift assay. Chromatin immunoprecipitation assays show the endogenous IkappaBalpha/epsilon, Gro-beta/gamma, and Naf-1 promoters directly bound NF-kappaB/Rel A in TNF-stimulated cells. Together, these studies systematically identify the direct NF-kappaB-dependent gene network downstream of TNF signaling, extending our knowledge of biological processes regulated by this pathway.
PMID	15722553
GEOID	GSE2624
AUTHORS	Tian B,Nowak DE,Jamaluddin M,Wang S,Brasier AR
CONTRIBUTOR	Arthur Liberzon
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 3
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	AF010316,AF050110,AF079529,AL021977,AL080156,J04111,L11329,L13740,L37882,L49169,M11717,M27826,M29039,M68891,S79639,S81914,U44975,U70426,U83981,U96876,X52541,X96401
GENE_SYMBOLS	PTGES,KLF10,PDE8B,PLA2G6,TIPARP,JUN,DUSP2,NR4A1,FZD2,FOSB,HSPA1A,TPTEP1,JUNB,GATA2,EXT1,IER3,KLF6,RGS16,PPP1R15A,INSIG1,EGR1,MNT
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