title: EDF-1 downregulates the CaM/Cn/NFAT signaling pathway during adipogenesis.
abstract: The endothelial differentiation factor-1 (EDF-1) is a calmodulin binding protein that regulates calmodulin-dependent enzymes. In endothelial cells, this factor can form a protein complex with calmodulin. We analyzed the relationship between this factor and the members of calmodulin/calcineurin/nuclear factor of activated T-cells (NFAT) signaling pathway during adipogenesis of 3T3-F442A cells. We found that the expression of edf1 is upregulated during early adipogenesis, whereas that of calcineurin gene is lowered, suggesting that this pathway should be downregulated to allow for adipogenesis to occur. We also found that EDF-1 associates with calmodulin and calcineurin, most likely inactivating calcineurin. Our results showed that EDF-1 inactivates the calmodulin/calcineurin/NFAT pathway via sequestration of calmodulin, during early adipogenesis, and we propose a mechanism that negatively regulates the activation of calcineurin through a complex formation between EDF-1 and calmodulin. This finding raises the possibility that modulating this pathway might offer some alternatives to regulate adipose biology.
authors: Department of Cell Biology, Center for Research and Advanced Studies-IPN, Apdo. Postal 14-740, México City 07000, Mexico.
authors: Carlos J
authors: CJ
authors: López-Victorio
authors: Cristina
authors: C
authors: Velez-delValle
authors: Alicia
authors: A
authors: Beltrán-Langarica
authors: Walid
authors: W
authors: Kuri-Harcuch
mesh_terms: D050156:Adipogenesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism*; D065095:Calcineurin Inhibitors; D002147:Calmodulin / Q000235:genetics / Q000378:metabolism*; D002148:Calmodulin-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D015536:Down-Regulation; D051379:Mice; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D065095:Calcineurin Inhibitors; D002147:Calmodulin; D002148:Calmodulin-Binding Proteins; C485470:Edf1 protein, mouse; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D019703:Calcineurin