Accumulation of sequence-specific RNA-binding proteins in the cytosol of activated T cells undergoing RNA degradation and apoptosis.
Engagement of the T cell antigen receptor (TCR) causes transformed T cell hybridomas to produce lymphokines and then die by an apoptotic mechanism. Here we show that these functional effects of TCR-mediated signaling are associated with the accumulation of several cytosolic mRNA-binding proteins including the previously described AU-A, -B, and -C proteins as well as a novel 70-kDa protein. The results indicate that the 70-kDa protein derived from a 90-kDa precursor present in unactivated T cells and that both proteins bound to two independent sites at the 3'-end of the interleukin-2 mRNA, one in the coding region and the other in an AU-rich segment of the 3'-untranslated region. Glucocorticoids, TCR engagement by monoclonal antibodies, pharmacologic mimics of TCR signaling, or high concentrations of protein or RNA synthesis inhibitors all induced apoptosis, the cytosolic appearance of the RNA-binding proteins, and an increased rate of RNA turnover. Moreover, drugs that interfere with TCR-mediated signals, such as cyclosporin A and staurosporin, prevented both apoptosis and the appearance of the RNA-binding factors. The fact that the accumulation of these factors occurred in the presence of inhibitors of transcription and translation suggested that these proteins are present in an inactive form in unstimulated T cells and are activated when apoptosis is induced.
Mondino
A
A
University of Minnesota Medical School, Department of Microbiology, Minneapolis 55455, USA.
Jenkins
M K
MK
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis; D001483:Base Sequence; D015152:Blotting, Northern; D010856:Columbidae; D016572:Cyclosporine / Q000494:pharmacology; D003574:Cytochrome c Group / Q000276:immunology; D003600:Cytosol / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006825:Hybridomas; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000096:biosynthesis; D008969:Molecular Sequence Data; D012313:RNA / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D015347:RNA Probes; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015183:Restriction Mapping; D015398:Signal Transduction; D019311:Staurosporine; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D014529:Uridine / Q000378:metabolism
D000470:Alkaloids; D000911:Antibodies, Monoclonal; D003574:Cytochrome c Group; D004791:Enzyme Inhibitors; D007376:Interleukin-2; D008222:Lymphokines; D015347:RNA Probes; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011948:Receptors, Antigen, T-Cell; D003609:Dactinomycin; D012313:RNA; D016572:Cyclosporine; D019311:Staurosporine; D014529:Uridine