AKT-ing via microRNA.
MicroRNAs are involved in almost every aspect of a mammalian cell's functionality, from stem cell differentiation to aging and pathogenesis; however, their role in immediate cell signaling is less defined. This has been recently demonstrated by the rapid increase or decrease of miR-21's abundance within minutes of activation or inhibition of the AKT pathway, respectively, which mediates its regulation of Fas ligand (FasL) and phosphatase and tensin homologue deleted on chromosome 10 (PTEN) expression, among other targets. Conversely, AKT induces rapid downregulation of miR-199a-5p to effect upregulation of hypoxia-inducible factor 1α Hif-1α and sirtuin 1 (Sirt1). This suggests that posttranscriptional mechanisms regulate miRNAs' processing and/or stability to induce the rapid fluctuation in their levels. In support, a growing number of studies are showing specific posttranscriptional regulation of miRNAs. The data potentially explain how AKT, and plausibly other signaling pathways, can specifically and promptly modulate a gene's translation while circumventing the need for transcription during transient signaling events. In this article we present our views regarding cell signaling via miRNAs.
Sayed
Danish
D
Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA.
Abdellatif
Maha
M
D000818:Animals; D045744:Cell Line, Tumor; D053222:Fas Ligand Protein / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism* / Q000502:physiology; D017202:Myocardial Ischemia / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000378:metabolism; D013552:Swine / Q000378:metabolism
D053222:Fas Ligand Protein; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C531408:mirn199 microRNA, human; D051057:Proto-Oncogene Proteins c-akt; D056564:Sirtuin 1
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