title: Germinal center-associated nuclear protein (GANP) has a phosphorylation-dependent DNA-primase activity that is up-regulated in germinal center regions.
abstract: Antigen stimulation induces a rapid proliferation of B cells for expansion of specific B cell clones and their further differentiation into antibody-producing cells in germinal centers of T-dependent antigen-immunized mice. Previously, we identified a 210-kDa germinal center-associated nuclear protein (GANP) that is up-regulated selectively in germinal centers and carries an MCM-binding domain in the carboxyl-terminal side. In addition, here, we found a region (from 414 to 550 aa) in GANP molecule that is slightly similar to the known DNA-primase component p49. The recombinant GANP fragment covering this region synthesizes RNA primers for extension by DNA polymerase I with single-stranded DNA templates in vitro. GANP DNA-primase activity is controlled by phosphorylation at Ser(502) that is induced by CD40-mediated signaling in vitro and in the germinal center B cells stimulated with antigen in vivo. Overexpression of ganp cDNA in Daudi B cells caused the increased DNA synthesis more than the levels of the mock-transfectants. These evidences suggested that the novel DNA-primase GANP is involved in regulation of cell proliferation of antigen-driven B cells in germinal centers.
authors.affiliation: Departments of Immunology and Surgery II, Kumamoto University School of Medicine, 2-2-1, Honjo, Kumamoto 860-0811, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kuwahara
authors.forename: S
authors.initials: S
authors.lastname: Tomiyasu
authors.forename: S
authors.initials: S
authors.lastname: Fujimura
authors.forename: K
authors.initials: K
authors.lastname: Nomura
authors.forename: Y
authors.initials: Y
authors.lastname: Xing
authors.forename: N
authors.initials: N
authors.lastname: Nishiyama
authors.forename: M
authors.initials: M
authors.lastname: Ogawa
authors.forename: S
authors.initials: S
authors.lastname: Imajoh-Ohmi
authors.forename: S
authors.initials: S
authors.lastname: Izuta
authors.forename: N
authors.initials: N
authors.lastname: Sakaguchi
mesh_terms: D000123:Acetyltransferases; D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D019915:DNA Primase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018858:Germinal Center / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011994:Recombinant Proteins; D000123:Acetyltransferases; C406825:MCM3AP protein, human; D019915:DNA Primase