Expression and biological activity of X-linked inhibitor of apoptosis (XIAP) in human malignant glioma
1999 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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Expression and biological activity of X-linked inhibitor of apoptosis (XIAP) in human malignant glioma
Wagenknecht, B.; Glaser, T.; Naumann, U.; Kugler, S. ; Isenmann, S.; Bähr, M. & Korneluk, R. G. et al. (1999)
Cell Death and Differentiation, 6(4) pp. 370-376. DOI: https://doi.org/10.1038/sj.cdd.4400503
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Details
- Authors
- Wagenknecht, B; Glaser, T.; Naumann, U.; Kugler, S. ; Isenmann, Stefan; Bähr, Mathias ; Korneluk, R. G.; Liston, P; Weller, M
- Abstract
- The inhibitor-of-apoptosis (IAP) proteins are a novel family of antiapoptotic proteins that are thought to inhibit cell death via direct inhibition of caspases, Here, we report that human malignant glioma cell lines express XIAP, HIAP-1 and HIAP-2 mRNA and proteins. NAIP was not expressed, IAP proteins were not cleaved during CD95 ligand (CD95L)-induced apoptosis, and loss of IAP protein expression was not responsible for the potentiation of CD95L-induced apoptosis when protein synthesis was inhibited, LN-18 cells are highly sensitive to CD95-mediated apoptosis, whereas LN-229 cells require co-exposure to CD95L and a protein synthesis inhibitor, CHX, to acquire sensitivity to apoptosis. Adenoviral XIAP gene transfer blocked caspase 8 and 3 processing in both cell lines in the absence of CHX, Apoptosis was blocked in the absence and in the presence of CHX. However, XIAP failed to block caspase 8 processing in LN-229 cells in the presence of CHX. There was considerable overlap of the effects of XIAP on caspase processing with those of BCL-2 and the viral caspase inhibitor crm-A, These data define complex regulatory mechanisms for CD95-mediated apoptosis in glioma cells and indicate that there may be a distinct pathway of death receptor-mediated apoptosis that is readily activated when protein synthesis is inhibited, The constitutive expression of natural caspase inhibitors may play a role in the resistance of these cells to apoptotic stimuli that directly target caspases, including radiochemotherapy and immune-mediated tumor cell lysis.
- Issue Date
- 1999
- Publisher
- Stockton Press
- Journal
- Cell Death and Differentiation
- ISSN
- 1350-9047