CpG-Specific Common Commitment in Caspase- Dependent and -Independent Cell Deaths

摘要

Cell death in mammals seems to have easpase-dependent and -independent pathways unlike that in Caenorhabditis delegans where CED-3 protease activation is the central command.A recent suggestion to define apoptosis as the caspase-dependent or caspasecommitted cell death form and leave cell death conmitted by other pathways as just cell death was meant to categorize the apparent divergence in mammalian cell deathe pathways.However,we show CpG oligonucleotides (ODN) blocking caspase-dependent fas(CD95) ligand-mediated apoptosis as well as caspase-independent etoposide-mediated apoptosis and etoposide-zVAD-mediated necrosis.CpG specificity was demonstrated by reversing the CpG motif or replacing it with a methylated motif (mCpG) which failed to inhibit.CpG ODN blocked CpG-specific DNA cleavage by rare-cutting NotI restriction,which produced a megabase cleavage pattern similar to that in the fasL and etoposide cell death inductions.GpG ODN inhibition ws similar to that by CpG-specific commitment point preceding caspase-dependent and -independent cell death pathways was suggested.CpG-specific modulation is a key epigenetic mechanism in genomic imprinting,resisting nuclease restriction,and patterning of chromation conformatons.It is now shown to have a powerful effect modulating cell death.