INDUCTION OF BCL-2 EXPRESSION BY PHOSPHORYLATED CREB PROTEINS DURING B-CELL ACTIVATION AND RESCUE FROM APOPTOSIS

摘要: Engagement of surface immunoglobulin on mature B cells leads to rescue from apoptosis and proliferation. Levels bcl-2 mRNA protein increase with cross-linking immunoglobulin. We have located the major positive regulatory region for control expression in 5'-flanking region. The can be divided into an upstream a downstream contains cyclic AMP-responsive element (CRE). show by antibody supershift experiments UV followed denaturing polyacrylamide gel electrophoresis that both CREB ATF family members bind this vitro. Mutations CRE site result loss binding also lead functional activity promoter transient-transfection assays. presence active implies regulation is linked signal transduction pathway cells. Treatment B-cell line BAL-17 either anti-immunoglobulin M or phorbol 12-myristate 13-acetate mediated site. more immature line, Ramos, esters rescues calcium-dependent apoptosis. increased following ester treatment, dependent These stimuli phosphorylation at serine 133. results activation kinase C rather than A. Although necessary, optimal induction requires participation element, suggesting alters its interaction element. appears play role during It possible responsible other cell types, particularly those which involved.