| First Author | Fritzius T | Year | 2008 |
| Journal | EMBO J | Volume | 27 |
| Issue | 9 | Pages | 1399-410 |
| PubMed ID | 18388859 | Mgi Jnum | J:225490 |
| Mgi Id | MGI:5693367 | Doi | 10.1038/emboj.2008.67 |
| Citation | Fritzius T, et al. (2008) Akt- and Foxo1-interacting WD-repeat-FYVE protein promotes adipogenesis. EMBO J 27(9):1399-410 |
| abstractText | 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 Czeta. 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 PPARgamma and C/EBPalpha, 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. |
