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Publication : miR-139 impacts FoxO1 action by decreasing FoxO1 protein in mouse hepatocytes.

First Author  Hasseine LK Year  2009
Journal  Biochem Biophys Res Commun Volume  390
Issue  4 Pages  1278-82
PubMed ID  19883627 Mgi Jnum  J:155599
Mgi Id  MGI:4414867 Doi  10.1016/j.bbrc.2009.10.135
Citation  Hasseine LK, et al. (2009) miR-139 impacts FoxO1 action by decreasing FoxO1 protein in mouse hepatocytes. Biochem Biophys Res Commun 390(4):1278-82
abstractText  FoxO1 is a master regulator of signaling pathways used by growth factors and hormones, including insulin. Its activity is regulated by changes in subcellular localization coupled to post-translational modifications such as phosphorylation, ubiquitination, and acetylation. As microRNAs have emerged as a newly identified means by which cells fine-tune gene expression, we hypothesized that they could regulate FoxO1. Since FoxO1 plays a key role in the liver, we used immortalized neonatal mouse hepatocytes to analyze the effects of potential microRNAs targeting FoxO1. We found that miR-139 targets FoxO1 mRNA directly and reduces the level of the protein without affecting transcript levels. This decrease in FoxO1 protein results in a decrease of its target genes, such as AdQR1, AdQR2 and Mttp. Our findings suggest a novel mode of FoxO1 regulation by which miR-139 could maintain the protein level of FoxO1 to preserve homeostatic regulation of its transcriptional activity in response to environmental stimuli.
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