Document Detail


Conserved MicroRNA miR-8/miR-200 and its target USH/FOG2 control growth by regulating PI3K.
MedLine Citation:
PMID:  20005803     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
How body size is determined is a long-standing question in biology, yet its regulatory mechanisms remain largely unknown. Here, we find that a conserved microRNA miR-8 and its target, USH, regulate body size in Drosophila. miR-8 null flies are smaller in size and defective in insulin signaling in fat body that is the fly counterpart of liver and adipose tissue. Fat body-specific expression and clonal analyses reveal that miR-8 activates PI3K, thereby promoting fat cell growth cell-autonomously and enhancing organismal growth non-cell-autonomously. Comparative analyses identify USH and its human homolog, FOG2, as the targets of fly miR-8 and human miR-200, respectively. USH/FOG2 inhibits PI3K activity, suppressing cell growth in both flies and humans. FOG2 directly binds to p85alpha, the regulatory subunit of PI3K, and interferes with the formation of a PI3K complex. Our study identifies two novel regulators of insulin signaling, miR-8/miR-200 and USH/FOG2, and suggests their roles in adolescent growth, aging, and cancer.
Authors:
Seogang Hyun; Jung Hyun Lee; Hua Jin; JinWu Nam; Bumjin Namkoong; Gina Lee; Jongkyeong Chung; V Narry Kim
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell     Volume:  139     ISSN:  1097-4172     ISO Abbreviation:  Cell     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-12-16     Completed Date:  2010-01-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1096-108     Citation Subset:  IM    
Affiliation:
School of Biological Sciences and National Creative Research Center, Seoul National University, Seoul, 151-742, Korea.
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / metabolism*
Adipose Tissue / metabolism
Animals
Body Size*
DNA-Binding Proteins / metabolism
Drosophila Proteins
Drosophila melanogaster / genetics,  physiology*
Humans
MicroRNAs / genetics,  metabolism*
Mutation
Transcription Factors / metabolism
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Drosophila Proteins; 0/MicroRNAs; 0/Transcription Factors; 0/ZFPM2 protein, human; 0/mir-8 microRNA, Drosophila; 0/u-shaped protein, Drosophila; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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