Molecular mechanisms of gene expression regulation by the apoptosis-promoting protein TIA-1.
TIA-1 and the related protein TIAR promote DNA fragmentation in digitonin-permeabilized thymocytes. These proteins contain RNA Recognition Motifs (RRMs) and bind uridine-rich sequences. These observations suggested that TIA-1/TIAR are pro-apoptotic factors that influence some aspect of RNA metabolism. Here we review recent data implicating TIA-1 as a regulator of translation of Tumor Necrosis Factor-alpha mRNA and as regulator of alternative splicing of a variety of pre-mRNAs, including those of the Fibroblast Growth Factor Receptor 2 and the Fas receptor. We also discuss how some of these activities could be integrated in the control of programmed of cell death.
Förch
P
P
Gene Expression Programme, European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
Valcárcel
J
J
D017398:Alternative Splicing; D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D053938:DNA Fragmentation; D053222:Fas Ligand Protein; D005786:Gene Expression Regulation; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D039102:Poly(A)-Binding Proteins; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D011506:Proteins; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D000074019:T-Cell Intracellular Antigen-1; D013950:Thymus Gland / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D039102:Poly(A)-Binding Proteins; D011506:Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D017468:Receptors, Fibroblast Growth Factor; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; D014409:Tumor Necrosis Factor-alpha; C496353:FGFR2 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2