Expression analysis and functional activity of interleukin-7 splice variants.
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.
Vudattu
N K
NK
Microbiology, Tumor and Cell Biology Center and SMI, Nobels Väg 18, Karolinska Institutet, Stockholm, Sweden.
Magalhaes
I
I
Hoehn
H
H
Pan
D
D
Maeurer
M J
MJ
D017398:Alternative Splicing / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D005091:Exons / Q000502:physiology; D006099:Granuloma / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015851:Interleukin-7 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D009928:Organ Specificity / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D050799:STAT5 Transcription Factor / Q000378:metabolism
C508605:IL7 protein, human; D015851:Interleukin-7; D020033:Protein Isoforms; D011994:Recombinant Proteins; D050799:STAT5 Transcription Factor