Gene, Protein, and in Silico Analyses of FoxO, an Evolutionary Conserved Transcription Factor in the Sea Urchin Paracentrotus lividus

FoxO is a member of the evolutionary conserved family of transcription factors containing a Forkhead box, involved in many signaling pathways of physiological and pathological processes. In mammals, mutations or dysfunctions of the <i>FoxO</i> gene have been implicated in diverse diseases. FoxO homologs have been found in some invertebrates, including echinoderms. We have isolated the FoxO cDNA from the sea urchin <i>Paracentrotus lividus</i> (<i>Pl-foxo</i>) and characterized the corresponding gene and mRNA. In silico studies showed that secondary and tertiary structures of <i>Pl-foxo</i> protein corresponded to the vertebrate FoxO3 isoform, with highly conserved regions, especially in the DNA-binding domain. A phylogenetic analysis compared the <i>Pl-foxo</i> deduced protein with proteins from different animal species and confirmed its evolutionary conservation between vertebrates and invertebrates. The increased expression of <i>Pl-foxo</i> mRNA following the inhibition of the PI3K signaling pathway paralleled the upregulation of <i>Pl-foxo</i> target genes involved in apoptosis or cell-cycle arrest events (<i>BI-1</i>, <i>Bax</i>, <i>MnSod</i>). In silico studies comparing molecular data from sea urchins and other organisms predicted a network of <i>Pl-foxo</i> protein-protein interactions, as well as identified potential miRNAs involved in <i>Pl-foxo</i> gene regulation. Our data may provide new perspectives on the knowledge of the signaling pathways underlying sea urchin development.