title: Akt- and Foxo1-interacting WD-repeat-FYVE protein promotes adipogenesis.
abstract: 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.
authors.affiliation: Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Fritzius
authors.forename: Karin
authors.initials: K
authors.lastname: Moelling
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D002352:Carrier Proteins; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; C514055:ProF protein, mouse; D034741:RNA, Small Interfering; D051057:Proto-Oncogene Proteins c-akt