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The tyrosine kinase Lck is required for CD95-independent caspase-8 activation and apoptosis in response to ionizing radiation
Department of Radiation Oncology, University of Tuebingen (Germany), Hoppe Seyler Str. 3, 72076 Tuebingen, Germany.
Department of Radiation Oncology, University of Tuebingen (Germany), Hoppe Seyler Str. 3, 72076 Tuebingen, Germany.
Department of Physiology, University of Tuebingen (Germany), Gmelinstrasse 5, 72076 Tuebingen, Germany.
Department of Radiation Oncology, University of Tuebingen (Germany), Hoppe Seyler Str. 3, 72076 Tuebingen, Germany.
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1999 (English)In: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 18, no 35, 4983-4992 p.Article in journal (Refereed) Published
Abstract [en]

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.
Keyword [en]
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
National Category
Cancer and Oncology Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-87025DOI: 10.1038/sj.onc.1202878ISI: 000082321700011PubMedID: 10490833OAI: oai:DiVA.org:liu-87025DiVA: diva2:584259
Available from: 2013-01-08 Created: 2013-01-08 Last updated: 2017-12-06

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Los, Marek Jan

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