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• W2091834996 abstract "T cells from patients with systemic lupus erythematosus express decreased levels of the T cell receptor-associated CD3 ζ chain, a feature directly linked to their aberrant function. The decrease in CD3ζ protein expression is in part due to decreased levels of functional wild type isoform of the 3′-untranslated region (UTR) of CD3ζ mRNA with concomitant increased levels of an unstable alternatively spliced isoform. In order to identify factors involved in the post-transcriptional regulation of CD3ζ, we performed mass spectrometric analysis of Jurkat T cell nuclear proteins “pulled down” by a CD3ζ 3′-UTR oligonucleotide, which identified the splicing protein alternative splicing factor/splicing factor 2 (ASF/SF2). We show for the first time that ASF/SF2 binds specifically to the 3′-UTR of CD3ζ and regulates expression of CD3ζ protein by limiting the production of the alternatively spliced isoform. During activation of human T cells, an increase in the wild type CD3ζ mRNA is associated with increased expression of ASF/SF2. Finally, we show a significant correlation between ASF/SF2 and CD3ζ protein levels in T cells from systemic lupus erythematosus patients. Thus, our results identify ASF/SF2 as a novel factor in the regulation of alternative splicing of the 3′-UTR of CD3ζ and protein expression in human T cells. T cells from patients with systemic lupus erythematosus express decreased levels of the T cell receptor-associated CD3 ζ chain, a feature directly linked to their aberrant function. The decrease in CD3ζ protein expression is in part due to decreased levels of functional wild type isoform of the 3′-untranslated region (UTR) of CD3ζ mRNA with concomitant increased levels of an unstable alternatively spliced isoform. In order to identify factors involved in the post-transcriptional regulation of CD3ζ, we performed mass spectrometric analysis of Jurkat T cell nuclear proteins “pulled down” by a CD3ζ 3′-UTR oligonucleotide, which identified the splicing protein alternative splicing factor/splicing factor 2 (ASF/SF2). We show for the first time that ASF/SF2 binds specifically to the 3′-UTR of CD3ζ and regulates expression of CD3ζ protein by limiting the production of the alternatively spliced isoform. During activation of human T cells, an increase in the wild type CD3ζ mRNA is associated with increased expression of ASF/SF2. Finally, we show a significant correlation between ASF/SF2 and CD3ζ protein levels in T cells from systemic lupus erythematosus patients. Thus, our results identify ASF/SF2 as a novel factor in the regulation of alternative splicing of the 3′-UTR of CD3ζ and protein expression in human T cells." @default.
• W2091834996 created "2016-06-24" @default.
• W2091834996 creator A5027542245 @default.
• W2091834996 creator A5059552004 @default.
• W2091834996 date "2010-04-01" @default.
• W2091834996 modified "2023-10-15" @default.
• W2091834996 title "Alternative Splicing Factor/Splicing Factor 2 Regulates the Expression of the ζ Subunit of the Human T Cell Receptor-associated CD3 Complex" @default.
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• W2091834996 doi "https://doi.org/10.1074/jbc.m109.091660" @default.
• W2091834996 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2857141" @default.
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