Analysis of the complex genomic structure of Bcl-x and its relationship to Bcl-x(gamma) expression after CD28-dependent costimulation.

The Bcl-x(gamma) cytosolic protein is essential for costimulatory activity after CD3/CD28 coligation. Here we delineate the Bcl-x(gamma)/Bcl-x genomic organization and the molecular mechanism that allows expression. We show that exon 4 of the Bcl-x gene encodes the unique C-terminal end of the Bcl-x(gamma) molecule while exons 5, 6, 7 and 8 are differentially transcribed to yield three alternative Bcl-x(gamma) 3' untranslated regions (UTR). CD28-dependent signals may increase levels of Bcl-x(gamma) protein through induction of an alternatively-spliced Bcl-x(gamma) 3' UTR that contains stem loop structures that stabilize Bcl-x(gamma) RNA. The ability receptor-induced signals to regulate the splicing pattern of the complex Bcl-x gene may allow T-cells to respond appropriately to antigenic stimuli.