title: Dephosphorylation of barrier-to-autointegration factor by protein phosphatase 4 and its role in cell mitosis.
abstract: Barrier-to-autointegration factor (BAF or BANF1) is highly conserved in multicellular eukaryotes and was first identified for its role in retroviral DNA integration. Homozygous BAF mutants are lethal and depletion of BAF results in defects in chromatin segregation during mitosis and subsequent nuclear envelope assembly. BAF exists both in phosphorylated and unphosphorylated forms with phosphorylation sites Thr-2, Thr-3, and Ser-4, near the N terminus. Vaccinia-related kinase 1 is the major kinase responsible for phosphorylation of BAF. We have identified the major phosphatase responsible for dephosphorylation of Ser-4 to be protein phosphatase 4 catalytic subunit. By examining the cellular distribution of phosphorylated BAF (pBAF) and total BAF (tBAF) through the cell cycle, we found that pBAF is associated with the core region of telophase chromosomes. Depletion of BAF or perturbing its phosphorylation state results not only in nuclear envelope defects, including mislocalization of LEM domain proteins and extensive invaginations into the nuclear interior, but also impaired cell cycle progression. This phenotype is strikingly similar to that seen in cells from patients with progeroid syndrome resulting from a point mutation in BAF.
authors.affiliation: From the Laboratory of Molecular Biology, NIDDK, and.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Zhuang
authors.forename: Elena
authors.initials: E
authors.lastname: Semenova
authors.forename: Dragan
authors.initials: D
authors.lastname: Maric
authors.forename: Robert
authors.initials: R
authors.lastname: Craigie
mesh_terms: D015153:Blotting, Western; D002453:Cell Cycle; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D008938:Mitosis; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012694:Serine / Q000235:genetics / Q000378:metabolism
chemical_list: C501959:BANF1 protein, human; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D012694:Serine; D017346:Protein Serine-Threonine Kinases; C109890:VRK1 protein, human; D010749:Phosphoprotein Phosphatases; C080406:protein phosphatase 4
keywords: BAF; BAF BANF1; BAF BANF1 PP4C; Cell Cycle; Chromosomes; Mitosis; Nuclear Membrane; Phosphorylation