Identification of a prominent nuclear protein associated with proliferation of normal and malignant B cells.
Experiments were undertaken to identify nuclear proteins that might be involved in regulation of the mitogenic process in B lymphocytes. Murine splenic B lymphocytes were purified and cultured with anti-Ig insolubilized onto Sepharose (anti-Ig/Sepharose) for 16 hr and labeled with [35S]methionine. Nuclei were isolated and the nuclear proteins were analyzed by two-dimensional gel electrophoresis. Anti-Ig/Sepharose induced a prominent increase in the synthesis and abundance of a 40 kDa/pI 5 nuclear protein (p40/pI-5). Inhibition of anti-Ig/Sepharose-induced mitogenesis by pretreatment of the cells with phorbol-12-myristate-13-acetate was associated with a specific inhibition (63%) of p40/pI-5. Subcellular fractionation experiments showed that p40/pI-5 is not detected in the soluble fraction of resting or activated B cells, indicating that this protein is located exclusively in the nucleus. Analysis of the expression of p40/pI-5 relative the cell cycle showed that the synthesis of this protein was increased during G1 phase and gradually reduced during S phase of the cell cycle. Abundant amounts of p40/pI-5 were also found in the rapidly proliferating B lymphoma cells, WEHI-231, and growth arrest of these cells by anti-mu was found to be associated with a marked inhibition (68%) of this protein. Taken collectively these results suggest that the nuclear protein p40/pI-5 may have an important role in regulation of the proliferation of normal and malignant B lymphocytes.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001402:B-Lymphocytes / Q000502:physiology*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000502:physiology; D007148:Immunoglobulin mu-Chains / Q000276:immunology; D007526:Isoelectric Point; D008213:Lymphocyte Activation / Q000187:drug effects; D008223:Lymphoma / Q000503:physiopathology; D051379:Mice; D008970:Molecular Weight; D011506:Proteins / Q000502:physiology*; D012313:RNA / Q000096:biosynthesis; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000888:Antibodies, Anti-Idiotypic; D007148:Immunoglobulin mu-Chains; D011506:Proteins; D011947:Receptors, Antigen, B-Cell; D012313:RNA; D013755:Tetradecanoylphorbol Acetate