title: Cyclin B1 expression regulated by cytoplasmic polyadenylation element binding protein in astrocytes.
abstract: Astrocytes are the most abundant cells in the brain, playing vital roles in neuronal survival, growth, and function. Understanding the mechanism(s) regulating astrocyte proliferation will have important implications in brain development, response to injury, and tumorigenesis. Cyclin B1 is well known to be a critical regulator of mitotic entry via its interaction with cyclin-dependent kinase 1. In rat astrocytes, we now show that the mRNA binding protein cytoplasmic polyadenylation element binding protein 1 (CPEB1) is associated with cyclin B1 mRNA and that this interaction is enriched at the centrosome. In addition, if growth-arrested astrocytes are stimulated to divide, CPEB1 is phosphorylated and cyclin B1 mRNA is polyadenylated, both hallmarks of CPEB1 activation, resulting in an increase in cyclin B1 protein. CPEB1 binding to mRNA initially inhibits translation; therefore, removing CPEB1 from mRNA should result in an increase in translation due to derepression. Indeed, when we either knocked down CPEB1 protein with siRNA or sequestered it from endogenous mRNA by expressing RNA containing multiple CPEB1 binding sites, cyclin B1 protein was increased and cell proliferation was stimulated. Our data suggest a mechanism wherein CPEB1 is bound and represses cyclin B1 mRNA translation until a signal to proliferate phosphorylates CPEB1, resulting in an increase in cyclin B1 protein and progression into mitosis. Our results demonstrate for the first time a role for CPEB1 in regulating cell proliferation in the brain.
authors.affiliation: Department of Pharmacology, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
authors.forename: Ki Chan
authors.initials: KC
authors.lastname: Kim
authors.forename: Won Jung
authors.initials: WJ
authors.lastname: Oh
authors.forename: Kwang Ho
authors.initials: KH
authors.lastname: Ko
authors.forename: Chan Young
authors.initials: CY
authors.lastname: Shin
authors.forename: David G
authors.initials: DG
authors.lastname: Wells
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018385:Centrosome / Q000378:metabolism; D056744:Cyclin B1 / Q000096:biosynthesis* / Q000235:genetics*; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D008297:Male; D026723:Polyadenylation / Q000235:genetics*; D020871:RNA Stability / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C539243:CPEB1 protein, rat; C534701:Ccnb1 protein, rat; D056744:Cyclin B1; D016601:RNA-Binding Proteins