Identification of a set of KSRP target transcripts upregulated by PI3K-AKT signaling.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Ruggiero
Tina
T
Istituto Nazionale per la Ricerca sul Cancro (IST), 16132 Genova, Italy. tina.ruggiero@istge.it <tina.ruggiero@istge.it>
Trabucchi
Michele
M
Ponassi
Marco
M
Corte
Giorgio
G
Chen
Ching-Yi
CY
al-Haj
Latifa
L
Khabar
Khalid S A
KS
Briata
Paola
P
Gherzi
Roberto
R
D000818:Animals; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000378:metabolism; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000378:metabolism; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation
D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D015534:Trans-Activators; C000630988:Hnrnpd protein, rat; C000630987:Hnrpd protein, mouse; C507913:Khsrp protein, mouse