Phosphoinositide 3-kinase regulates a subset of interferon-alpha-stimulated genes
| Autor: | Dominic Chan, Linn Hjortsberg, Velmurugesan Arulampalam, Martin Corcoran, Dan Grandér, Magnus Nordenskjöld, Lena Thyrell, Katja Pokrovskaja, Charlotta Lindvall |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Morpholines
Gene Expression Apoptosis Suppressor of Cytokine Signaling Proteins Biology chemistry.chemical_compound Phosphatidylinositol 3-Kinases Transcription (biology) Genes Reporter Complementary DNA Cell Line Tumor Gene expression Consensus Sequence Humans LY294002 Enzyme Inhibitors Luciferases Promoter Regions Genetic Gene Transcription factor PI3K/AKT/mTOR pathway Oligonucleotide Array Sequence Analysis Phosphoinositide-3 Kinase Inhibitors Regulation of gene expression Base Sequence Computational Biology Interferon-alpha Cell Biology Molecular biology STAT Transcription Factors chemistry Gene Expression Regulation Chromones Suppressor of Cytokine Signaling 3 Protein Signal Transduction |
| Zdroj: | Karolinska Institutet |
| ISSN: | 0014-4827 |
| Popis: | IFNalpha activates JAK-STAT signaling, followed by up-regulation of a cohort of genes. Also the PI3K pathway is activated by IFNalpha, but the significance of this activation for IFN-induced gene expression and biological functions remains unclear. We used a cDNA microarray to identify IFNalpha target genes whose expression is dependent on PI3K signaling. cDNAs from U266-1984 cells, untreated and IFNalpha-treated with or without PI3K inhibitor, Ly294002, was used in hybridization to a microarray representing 7000 genes. Among the 260 genes stimulated by IFNalpha, the expression of 95.4% was not affected by the presence of Ly294002. Luciferase reporter assays using consensus IFN-stimulated sequences confirmed that general regulation of transcription by IFNalpha is not altered by Ly294002. Up-regulation of 10 genes (3.8%) was affected in the presence of Ly294002. Bioinformatic analysis revealed the presence of consensus sequences of both STAT-specific and the PI3K pathway-regulated transcription factors, further suggesting that these genes are regulated by both pathways. We have recently shown that IFNalpha-induced apoptosis in the myeloma cell line U266-1984 was efficiently blocked by inhibition of PI3K. Therefore we suggest that the genes that are regulated by both the STAT and the PI3K pathways by IFNalpha in these cells may be specifically involved in the induction of apoptosis. |
| Databáze: | OpenAIRE |
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