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 Differentiation6(4) pp. 370​-376​.​ DOI: https://doi.org/10.1038/sj.cdd.4400503 

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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

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