Systematic name M2295
Brief description Genes down-regulated in I/11 erythroblast cells upon expression of an activated form of FOXO3 [GeneID=2309].
Full description or abstract The cooperation of stem cell factor (SCF) and erythropoietin (Epo) is required to induce renewal divisions in erythroid progenitors, whereas differentiation to mature erythrocytes requires the presence of Epo only. Epo and SCF activate common signaling pathways such as the activation of protein kinase B (PKB) and the subsequent phosphorylation and inactivation of Foxo3a. In contrast, only Epo activates Stat5. Both Foxo3a and Stat5 promote erythroid differentiation. To understand the interplay of SCF and Epo in maintaining the balance between renewal and differentiation during erythroid development, we investigated differential Foxo3a target regulation by Epo and SCF. Expression profiling revealed that a subset of Foxo3a targets was not inhibited but was activated by Epo. One of these genes was Cited2. Transcriptional control of Epo/Foxo3a-induced Cited2 was studied and compared with that of the Epo-repressed Foxo3a target Btg1. We show that in response to Epo, the allegedly growth-inhibitory factor Foxo3a associates with the allegedly growth-stimulatory factor Stat5 in the nucleus, which is required for Epo-induced Cited2 expression. In contrast, Btg1 expression is controlled by the cooperation of Foxo3a with cyclic AMP- and Jun kinase-dependent Creb family members. Thus, Foxo3a not only is an effector of PKB but also integrates distinct signals to regulate gene expression in erythropoiesis.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 17353275   Authors: Bakker WJ,Dijk van TB,Amelsvoort Parren-van M,Kolbus A,Yamamoto K,Steinlein P,Verhaak RG,Mak TW,Beug H,L÷wenberg B,Lindern von M
Exact source Suppl. file 'cluster_list_Bakker.xls': cluster B, C
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(show 51 gene sets from the same authors)
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Organism Mus musculus
Contributed by Arthur Liberzon (MSigDB Team)
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Version history 3.1: First introduced

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