Ruggiero, T. et al. Identification of a set of KSRP target transcripts up-regulated by PI3K-AKT signaling. BMC Mol. Biol. 8, 28-43

University of Alabama at Birmingham, Birmingham, Alabama, United States
BMC Molecular Biology (Impact Factor: 2.19). 02/2007; 8(1):28. DOI: 10.1186/1471-2199-8-28
Source: PubMed


KSRP is a AU-rich element (ARE) binding protein that causes decay of select sets of transcripts in different cell types. We have recently described that phosphatidylinositol 3-kinase/AKT (PI3K-AKT) activation induces stabilization and accumulation of the labile beta-catenin mRNA through an impairment of KSRP function.
Aim of this study was to identify additional KSRP targets whose stability and steady-state levels are enhanced by PI3K-AKT activation. First, through microarray analyses of the AU-rich transcriptome in pituitary alphaT3-1 cells, we identified 34 ARE-containing transcripts upregulated in cells expressing a constitutively active form of AKT1. In parallel, by an affinity chromatography-based technique followed by microarray analyses, 12 mRNAs target of KSRP, additional to beta-catenin, were identified. Among them, seven mRNAs were upregulated in cells expressing activated AKT1. Both steady-state levels and stability of these new KSRP targets were consistently increased by either KSRP knock-down or PI3K-AKT activation.
Our study identified a set of transcripts that are targets of KSRP and whose expression is increased by PI3K-AKT activation. These mRNAs encode RNA binding proteins, signaling molecules and a replication-independent histone. The increased expression of these gene products upon PI3K-AKT activation could play a role in the cellular events initiated by this signaling pathway.

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    • "HuR, an RNA binding protein, is the only known factor able to stabilize b-catenin mRNA and to enhance b-catenin protein production, and it contributes to b-catenin accumulation in colon cancer (Lopez de Silanes et al, 2003). On the other hand, factors that destabilize b-catenin mRNA or reduce b-catenin protein production have also been identified, including KSRP, eIF6 and Quaking (Bikkavilli & Malbon, 2010; Gherzi et al, 2006; Ji et al, 2008; Ruggiero et al, 2007; Yang et al, 2010). Compared with our understanding of b-catenin degradation, the regulation of b-catenin protein production is far less clear and therefore requires further investigation. "
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    • "Coimmunoprecipitation experiments have demonstrated that various ARE-BPs can directly interact with one another including: HuR/AUF1 [10]; HuR/TIA-1 [11,12]; KSRP/AUF1 [13] and KSRP/TIA-1 [14]. What cannot be determined by immunoprecipitation, however, is where within the cell these interactions are taking place. "
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