Premium
Akt‐ and Foxo1‐interacting WD‐repeat‐FYVE protein promotes adipogenesis
Author(s) -
Fritzius Thorsten,
Moelling Karin
Publication year - 2008
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2008.67
Subject(s) - biology , adipogenesis , foxo1 , protein kinase b , microbiology and biotechnology , phosphorylation , genetics , gene
We have previously identified a protein, consisting of seven WD‐repeats, forming a putative β‐ pro peller, and an F YVE 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 Cζ. 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 PPARγ and C/EBPα, 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.