C. Belka et al., The tyrosine kinase Lck is required for CD95-independent caspase-8 activation and apoptosis in response to ionizing radiation, ONCOGENE, 18(35), 1999, pp. 4983-4992
Induction of apoptosis is a hallmark of cytostatic drug and radiation-induc
ed cell death in human lymphocytes and lymphoma cells. However, the mechani
sms 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 radiat
ion induced cleavage pattern of procaspase-8 into mature caspase-8 resemble
d that following CD95 crosslinking and resulted in cleavage of the proapopt
otic substrate BID. Overexpression of dominant-negative caspase-8 interfere
d with radiation-induced apoptosis, Caspase-8 activation by ionizing radiat
ion was not observed in cells genetically defective for the Src-like tyrosi
ne 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 casp
ase-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.