1. Expression analysis and functional activity of interleukin-7 splice variants.
- Author
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Vudattu NK, Magalhaes I, Hoehn H, Pan D, and Maeurer MJ
- Subjects
- CD4-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes metabolism, Cell Line, Tumor, Cell Survival drug effects, Cell Survival physiology, Exons physiology, Granuloma genetics, Granuloma metabolism, Humans, Interleukin-7 genetics, Interleukin-7 pharmacology, Organ Specificity physiology, Phosphorylation drug effects, Phosphorylation physiology, Protein Isoforms biosynthesis, Protein Isoforms genetics, Protein Isoforms pharmacology, Recombinant Proteins biosynthesis, Recombinant Proteins genetics, Recombinant Proteins pharmacology, STAT5 Transcription Factor metabolism, Alternative Splicing physiology, Interleukin-7 biosynthesis
- Abstract
Alternative splicing results in multiple protein isoforms derived from a single gene. The magnitude of this process ranges from a complete loss of function to gain of new function. We examined, as a paradigm, alternative splicing of the non-redundant human cytokine, interleukin-7 (IL-7). We show that extensive IL-7 splicing in human tissues of different histology, including MTB+ granuloma lesions, transformed tissue and tumor cell lines. IL-7 splice variants were expressed as recombinant proteins. A differentially spliced IL-7 isoform, lacking exon 5, leads to STAT-5 phosphorylation in CD4+ and CD8+ T cells, promotes thymocyte maturation and T-cell survival. Human tumor lesions show aberrant IL-7 isoform expression, as compared with the autologous, non-transformed tissue. Alternatively spliced cytokines, such as IL-7, represent candidates for diagnostics and therapeutic interventions.
- Published
- 2009
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