TRAIL-β and TRAIL-γ: two novel splice variants of the human TNF-related apoptosis-inducing ligand (TRAIL) without apoptotic potential
| Autor: | Thomas Krieg, Uwe Ramp, Helmut E. Gabbert, Arthur M. Krieg, Claus-Dieter Gerharz, B Fang, Michael Wenzel, M Schmitt, Csaba Mahotka |
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| Rok vydání: | 2003 |
| Předmět: |
Cytoplasm
Cancer Research Programmed cell death Molecular Sequence Data TRAIL Biology Ligands neoplastic cells TNF-Related Apoptosis-Inducing Ligand alternative splicing Exon Tumor Cells Cultured Humans splice fas Receptor Frameshift Mutation Carcinoma Renal Cell Membrane Glycoproteins Base Sequence Tumor Necrosis Factor-alpha Alternative splicing apoptosis Genetics and Genomics Exons Fas receptor Kidney Neoplasms Oncology Apoptosis Immunology Cancer research Neoplastic cell Ectopic expression Apoptosis Regulatory Proteins |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/sj.bjc.6600772 |
| Popis: | Tumour necrosis factor (TNF) related apoptosis-inducing ligand (TRAIL/APO2L) is a recently identified member of the TNF family, which induces programmed cell death in a variety of neoplastic cell types, but not in most nonneoplastic cells. In this study, we report on the identification of two novel alternative splice variants of TRAIL in neoplastic and non-neoplastic human cells lacking either exon 3 (TRAIL-beta) or exons 2 and 3 (TRAIL-gamma). In both splice variants, loss of exon 3 resulted in a frame shift generating a stop codon with consecutive extensive truncation in the extracellular domain. Ectopic expression revealed a loss of proapoptotic potential for both alternative splice variants. In contrast to the predominantly cytoplasmatic localisation of GFP-tagged TRAIL-alpha and TRAIL-beta, TRAIL-gamma showed an additional association with the cell surface and nuclear membrane. In conclusion, alternative splicing might be involved in fine tuning of TRAIL-induced apoptosis and underlines the complexity of the TRAIL system. |
| Databáze: | OpenAIRE |
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