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| Subject Categories: Differentiation & Death | Cellular Metabolism |
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| The EMBO Journal
(2008) 27, 1399–1410, doi:10.1038/emboj.2008.67 Published online 3 April 2008 |
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| Akt- and Foxo1-interacting WD-repeat-FYVE protein promotes adipogenesis |
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| Thorsten Fritzius and Karin Moelling |
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Institute of Medical Virology, University of Zurich, Zurich, Switzerland To whom correspondence should be addressed Karin Moelling, Institute of Medical Virology, University of Zurich, Gloriastrasse 30, Zurich 8006, Switzerland. Tel.: +41 44 634 26 52; Fax: +41 44 634 49 67; E-mail: moelling@immv.uzh.ch Received 26 October 2007; Accepted 6 March 2008; Published online 3 April 2008. |
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| Abstract |
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We have previously identified a protein, consisting of seven WD-repeats, forming a putative  -propeller, and an FYVE domain, ProF, which is highly expressed in 3T3-L1 cells, a cell line that can be differentiated into adipocytes. We recently found ProF to interact with the kinases Akt and protein kinase C . Here we demonstrate that ProF is a positive regulator of adipogenesis. Knockdown of ProF by RNA interference leads to decreased adipocyte differentiation. This is shown by reduced lipid accumulation, decreased expression of the differentiation markers PPAR and C/EBP , and reduced glucose uptake in differentiated cells. Furthermore, ProF overexpression leads to increased adipogenesis. ProF binds to the transcription factor Foxo1 (Forkhead box O1), a negative regulator of insulin action and adipogenesis, and facilitates the phosphorylation and thus inactivation of Foxo1 by Akt. Additionally, dominant-negative Foxo1 restores adipogenesis in ProF knockdown cells. Thus, ProF modulates Foxo1 phosphorylation by Akt, promoting adipocyte differentiation. Furthermore, ProF might be involved in metabolic disorders such as diabetes. |
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| Keywords: adipogenesis, Akt, Foxo1, PPAR, ProF |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHAkt- and Foxo1-interacting WD-repeat-FYVE protein promotes adipogenesis The EMBO Journal Article Hzf regulates adipogenesis through translational control of C/EBPα The EMBO Journal Article (21 May 2008) Hzf regulates adipogenesis through translational control of C/EBPα The EMBO Journal Article Cathepsin L activity controls adipogenesis and glucose tolerance Nature Cell Biology Letter (01 Aug 2007) |
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