6533b86dfe1ef96bd12c972f
RESEARCH PRODUCT
Expression analysis and functional activity of interleukin-7 splice variants.
D PanIsabelle MagalhaesNalini K. VudattuMarkus MaeurerH Hoehnsubject
Gene isoformCD4-Positive T-LymphocytesCell SurvivalImmunologyBiologyCD8-Positive T-LymphocytesExonCell Line TumorGeneticsSTAT5 Transcription FactorHumansProtein IsoformssplicePhosphorylationGenetics (clinical)GranulomaInterleukin-7Alternative splicingInterleukinExonsMolecular biologyRecombinant ProteinsCell biologyThymocyteAlternative SplicingOrgan SpecificityRNA splicingCD8description
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2008-12-18 | Genes and immunity |