Translational upregulation of X-linked inhibitor of apoptosis (XIAP) increases resistance to radiation induced cell death.
Inhibitory regulators of apoptosis play a critical role in the responsiveness of tumour cells to cytotoxic agents. The X-linked inhibitor of apoptosis protein (XIAP) is a member of a novel family of Inhibitor of Apoptosis (IAP) proteins. Here we show that acute low dose ionizing irradiation results in the translational upregulation of XIAP that correlates with an increased resistance to radiation in non-small cell lung carcinoma. This upregulation is mediated by an internal ribosome binding mechanism via an IRES element located within a XIAP 5' UTR. Transient overexpression of XIAP rendered human carcinoma cells resistant to low dose gamma-irradiation. By contrast, the antisense targeting of XIAP resulted in increased cell death following irradiation advocating a distinct role for XIAP in radiation resistant phenotype of human cancers. Oncogene (2000) 19, 4174 - 4177
Holcik
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Apoptogen Inc., 401 Smyth Road, Ottawa, Ontario, K1H 8L1, Canada.
Yeh
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C
Korneluk
R G
RG
Chow
T
T
D020121:5' Untranslated Regions; D016375:Antisense Elements (Genetics); D017209:Apoptosis; D005720:Gamma Rays; D006801:Humans; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000235:genetics; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D051636:X-Linked Inhibitor of Apoptosis Protein
D020121:5' Untranslated Regions; D016375:Antisense Elements (Genetics); D011506:Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human