Apoptosis
or programmed cell death is induced in cells by a group
of death domain containing receptors. Binding of ligand
to these receptors sends signals that activate members
of the caspase family of proteases. The signals ultimately
cause degradation of chromosomal DNA by activating DNase.
TRAIL (TNF related apoptosis induced ligand) or Apo 2L
initiates apoptosis of tumor cells by binding to either
of its receptors, DR4 or DR5. These receptors consist of
an extracellular TRAIL binding domain and a cytoplasmic "death
domain". In addition, two decoy receptors for TRAIL
have also been identified. These receptors, designated
DcR1 and DcR2, lack the death domain. Binding of TRAIL
to either of these receptors, therefore, does not transmit
the death signal. Thus, these receptors represent a novel
way of regulating cell sensitivity to a pro-apoptotic cytokine
at the cell surface. DcR2 is widely expressed, in particular
in fetal kidney, lung and liver, and in adult testis and
liver. It is also expressed in peripheral blood leukocytes,
colon and small intestine, ovary, prostate, thymus, spleen,
pancreas, kidney, lung, placenta and heart.
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