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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Li, Xiaohong Holland, William Moresco, Eva Marie Y. Shelton, John M. Zhan, Xiaoming Won, Sungyong Liu, Chen Ali, Aktar Beutler, Bruce Chen, Zhe Tomisato, Wataru |
| Description | Author Affiliation: Chen Z ( Center for Genetics of Host Defense.); Holland W ( Department of Internal Medicine, Touchstone Diabetes Center.); Shelton JM ( Department of Internal Medicine, Division of Cardiology.); Ali A ( Department of Internal Medicine, and.); Zhan X ( Center for Genetics of Host Defense.); Won S ( Center for Genetics of Host Defense.); Tomisato W ( Center for Genetics of Host Defense.); Liu C ( Department of Internal Medicine, Division of Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, TX 75390.); Li X ( Center for Genetics of Host Defense.); Moresco EM ( Center for Genetics of Host Defense.); Beutler B ( Center for Genetics of Host Defense, bruce.beutler@utsouthwestern.edu.); |
| Abstract | Sterile alpha motif domain containing protein 4 (Samd4) is an RNA binding protein that mediates translational repression. We identified a Samd4 missense mutation, designated supermodel, that caused leanness and kyphosis associated with myopathy and adipocyte defects in C57BL/6J mice. The supermodel mutation protected homozygous mice from high fat diet-induced obesity, likely by promoting enhanced energy expenditure through uncoupled mitochondrial respiration. Glucose tolerance was impaired due to diminished insulin release in homozygous mutant mice. The defects of metabolism in supermodel mice may be explained by dysregulated mechanistic target of rapamycin complex 1 (mTORC1) signaling, evidenced by hypophosphorylation of 4E-BP1 and S6 in muscle and adipose tissues of homozygous mice. Samd4 may interface with mTORC1 signaling through an interaction with 14-3-3 proteins and with Akt, which phosphorylates Samd4 in vitro. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 20 |
| Volume Number | 111 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2014-05-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Multiprotein Complexes Metabolism Mutation Repressor Proteins Genetics Signal Transduction TOR Serine-Threonine Kinases 14-3-3 Proteins Adipocytes Cytology Amino Acid Motifs Animals Body Composition Glucose Glucose Tolerance Test Mice Mice, Inbred C57BL Mutagenesis Phenotype Phosphorylation RNA-Binding Proteins Physiology Research Support, N.I.H., Extramural Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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