The tyrosine kinase Lck is required for CD95-independent caspase-8 activation and apoptosis in response to ionizing radiation
1999 (English)In: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 18, no 35, 4983-4992 p.Article in journal (Refereed) Published
Induction of apoptosis is a hallmark of cytostatic drug and radiation-induced cell death in human lymphocytes and lymphoma cells. However, the mechanisms leading to apoptosis are not well understood. We provide evidence that ionizing radiation induces a rapid activation of caspase-8 (FLICE) followed by apoptosis independently of CD95 ligand/receptor interaction. The radiation induced cleavage pattern of procaspase-8 into mature caspase-8 resembled that following CD95 crosslinking and resulted in cleavage of the proapoptotic substrate BID. Overexpression of dominant-negative caspase-8 interfered with radiation-induced apoptosis, Caspase-8 activation by ionizing radiation was not observed in cells genetically defective for the Src-like tyrosine kinase Lck, Cells lacking Lck also displayed a marked resistance towards apoptosis induction upon ionizing radiation. After retransfection of Lck, caspase-8 activation and the capability to undergo apoptosis in response to ionizing radiation was restored. We conclude that radiation activates caspase-8 via an Lck-controlled pathway independently of CD95 ligand expression, This is a novel signaling event required for radiation induced apoptosis in T lymphoma cells.
Place, publisher, year, edition, pages
Nature Publishing Group, 1999. Vol. 18, no 35, 4983-4992 p.
Apoptosis, b-cells, caspase-8/FLICE, cytochrome-c, death, drug-induced apoptosis, fas-induced apoptosis, Lck, leukemia-cells, ligand expression, lymphoma, phosphorylation, sh2 domain, t-cells, tyrosine kinase
Cancer and Oncology Biochemistry and Molecular Biology
IdentifiersURN: urn:nbn:se:liu:diva-87025DOI: 10.1038/sj.onc.1202878ISI: 000082321700011PubMedID: 10490833OAI: oai:DiVA.org:liu-87025DiVA: diva2:584259