Analysis of the complex genomic structure of Bcl-x and its relationship to Bcl-xγ expression after CD28-dependent costimulation
Harvard University, Cambridge, Massachusetts, United States Molecular Immunology
(Impact Factor: 2.97).
10/2002; 39(1-2):45-55. DOI: 10.1016/S0161-5890(02)00049-4
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.
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