Gene Set: TSENG_IRS1_TARGETS_DN

Standard name TSENG_IRS1_TARGETS_DN
Systematic name M13907
Brief description Down-regulated in brown preadipocytes with IRS1 [GeneID=3667] knockout vs wild type controls; the knockouts have severe defects in adipocyte differentiation.
Full description or abstract The insulin/IGF-1 (insulin-like growth factor 1) signalling pathway promotes adipocyte differentiation via complex signalling networks. Here, using microarray analysis of brown preadipocytes that are derived from wild-type and insulin receptor substrate (Irs) knockout animals that exhibit progressively impaired differentiation, we define 374 genes/expressed-sequence tags whose expression in preadipocytes correlates with the ultimate ability of the cells to differentiate. Many of these genes, including preadipocyte factor-1 (Pref-1) and multiple members of the Wnt signalling pathway, are related to early adipogenic events. Necdin is also markedly increased in Irs knockout cells that cannot differentiate, and knockdown of necdin restores brown adipogenesis with downregulation of Pref-1 and Wnt10a expression. Insulin receptor substrate proteins regulate a necdin-E2F4 interaction that represses peroxisome-proliferator-activated receptor gamma (PPARgamma) transcription via a cyclic AMP response element binding protein (CREB)-dependent pathway. Together these define a key signalling network that is involved in brown preadipocyte determination.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 15895078   Authors: Tseng YH,Butte AJ,Kokkotou E,Yechoor VK,Taniguchi CM,Kriauciunas KM,Cypess AM,Niinobe M,Yoshikawa K,Patti ME,Kahn CR
Exact source Table 1S: IRS-1 KO / WT < 1
Related gene sets (show 3 additional gene sets from the source publication)

(show 1 gene sets from the same authors)
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Organism Mus musculus
Contributed by John Newman (University of Washington)
Source platform MG_U74Av2
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Compendia expression profiles Human tissue compendium (Novartis)
NCI-60 cell lines (National Cancer Institute)
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Version history 3.0: Renamed from IRS1_KO_ADIP_DN

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