Dataset Information


Transcription profiling of human CD4+ leukemia Jurkat T-cells in which the PI3K pathway is constitutively turned-on and FOXO1 transcriptional activity strongly repressed

ABSTRACT: One major effect of PI3-kinase activation downstream of the serine/threonine kinase Akt is the phosphorylation of the transcription factor FOXO1 and its neutralization. FOXO1 has several ubiquitous targets genes in many cell types that control cell quiescence, oxydative stress or apoptosis. However, it has been demonstrated that FOXO1 also has specific targets depending of the cellular context. The role of FOXO1 to regulate specific genes in T lymphocytes has not been investigated yet. To examine this point, we used the CD4+ leukemia Jurkat T-cell line, in which the PI3K pathway is constitutively turned-on and FOXO1 transcriptional activity strongly repressed. These cells were transduced with lentiviruses coding for a constitutively active form of FOXO1 fused to GFP and having the three AKT phosphorylation sites mutated to alanine (FOXO1-AAA-GFP) to restore its transcriptional activity. GFP-transduced cells were used as a control and the gene activation levels in the two cell populations analyzed 48 hours post-infection.

ORGANISM(S): Homo sapiens  

DISEASE(S): Leukemia

SUBMITTER: Philippe Dessen  

PROVIDER: E-TABM-391 | ArrayExpress | 2008-12-01


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FOXO1 regulates L-Selectin and a network of human T cell homing molecules downstream of phosphatidylinositol 3-kinase.

Fabre Stéphanie S   Carrette Florent F   Chen Jing J   Lang Valérie V   Semichon Monique M   Denoyelle Christine C   Lazar Vladimir V   Cagnard Nicolas N   Dubart-Kupperschmitt Anne A   Mangeney Marianne M   Fruman David A DA   Bismuth Georges G  

Journal of immunology (Baltimore, Md. : 1950) 20080901 5

In T cells, the PI3K pathway promotes proliferation and survival induced by Ag or growth factors, in part by inactivating the FOXO transcription factor 1. We now report that FOXO1 controls the expression of L-selectin, an essential homing molecule, in human T lymphocytes. This control is already operational in unprimed T cells and involves a transcriptional regulation process that requires the FOXO1 DNA-binding domain. Using transcriptional profiling, we demonstrate that FOXO1 also increases tra  ...[more]

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