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.
Yang
Xiao-Feng
XF
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Ye
Qunrui
Q
Press
Barry
B
Han
Rui-Zhu
RZ
Bassing
Craig H
CH
Sleckman
Barry P
BP
Alt
Frederick W
FW
Cantor
Harvey
H
D020413:3' Untranslated Regions / Q000502:physiology; D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D018106:CD28 Antigens / Q000502:physiology*; D005091:Exons; D007438:Introns; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics*; D013601:T-Lymphocytes / Q000378:metabolism; D014158:Transcription, Genetic; D051020:bcl-X Protein
D020413:3' Untranslated Regions; C494812:Bcl2l1 protein, mouse; D018106:CD28 Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein