title: Phosphorylation of the large subunit of replication factor C is associated with adipocyte differentiation.
abstract: Adipocyte differentiation is an ordered multistep process requiring the sequential activation of several groups of adipogenic transcription factors, including CCAAT/enhancer-binding protein-alpha and peroxisome proliferator-activated receptor-gamma, and coactivators. Here we show that replication factor C 140, which was known to act as a coactivator for CCAAT/enhancer-binding protein-alpha in our previous study, was phosphorylated on the proliferating cell nuclear antigen-bindng domain during the adipocyte differentiation process. Calmodulin-dependent protein kinase II was responsible for phosphorylating replication factor C 140 in the process of adipocyte differentiation. Ser518 of replication factor C 140 was identified as a major target of calmodulin-dependent protein kinase II phosphorylation in vitro. Calmodulin-dependent protein kinase II inhibitor attenuated phosphorylation of replication factor C 140 by differentiation inducers and blocked replication factor C 140-derived transcriptional activation. Taken together, these findings demonstrate that calmodulin-dependent protein kinase II signaling leads the cooperative transactivation of CCAAT/enhancer-binding protein-alpha and replication factor C 140 through an increase in replication factor C 140 phosphorylation, and subsequently enhances the transcriptional activation of target genes involved in adipocyte differentiation.
authors.affiliation: Department of Molecular Biology, Pusan National University, Jang-Jeon Dong, Keum-Jeong Gu, Busan 607-935, Korea.
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Park
authors.forename: Min Young
authors.initials: MY
authors.lastname: Lee
authors.forename: Jung Hae
authors.initials: JH
authors.lastname: Choi
authors.forename: Hyun Kook
authors.initials: HK
authors.lastname: Cho
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.forename: Ung Suk
authors.initials: US
authors.lastname: Yang
authors.forename: JaeHun
authors.initials: J
authors.lastname: Cheong
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002454:Cell Differentiation; D017930:Genes, Reporter; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry* / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D051818:Replication Protein C / Q000737:chemistry* / Q000378:metabolism; D014162:Transfection
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D021122:Protein Subunits; D034741:RNA, Small Interfering; D008156:Luciferases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D051818:Replication Protein C