期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 390, 期 4, 页码 1278-1282出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2009.10.135
关键词
MicroRNA; FoxO; Liver
资金
- Institut National de la Sante et de la Recherche Medicale
- Universite de Nice-Sophia-Antipolis
- Conseil Regional Provence-Alpes-Cote d'Azur
- Conseil General des Alpes-Maritimes
- European Community FP6 EUGENE2 [LSHM-CT-2004-512013]
- European Foundation for the Study of Diabetes/Merck Sharp and Dohme
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. (C) 2009 Elsevier Inc. All rights reserved.
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