Akt- and Foxo1-interacting WD-repeat-FYVE protein promotes adipogenesis

doi:doi:10.1038/emboj.2008.67

Article

The EMBO Journal (2008) 27, 1399 - 1410
doi:10.1038/emboj.2008.67

Published online: 3 April 2008

Subject Categories:
- Differentiation and Death | Cellular Metabolism

Akt- and Foxo1-interacting WD-repeat-FYVE protein promotes adipogenesis

Thorsten Fritzius¹ and Karin Moelling¹

Institute of Medical Virology, University of Zurich, Zurich, Switzerland

Correspondence to:

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

We have previously identified a protein, consisting of seven WD-repeats, forming a putative beta -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 zeta . 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 gamma and C/EBP alpha , 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.