Caspase 8

             Caspase 8

 

 


 
            

        

 

A key function of human granzyme B (GrB) is to induce apoptosis of target cells, in conjunction with perforin. The RAH allele is the first documented variant of the human GrB gene, and occurs at frequency of 25-30%. It encodes three amino acid substitutions (Q48R, P88A, Y245H). It was initially reported that RAH GrB is incapable of inducing apoptosis, but here we show that it has essentially identical proteolytic and cytotoxic properties to wild type GrB. Recombinant RAH and wild type GrB cleave peptide substrates with similar kinetics, are both capable of cleaving Bid and procaspase 3, and are equally inhibited by an endogenous regulator of GrB, PI-9. Furthermore, cytotoxic lymphocytes from RAH heterozygotes and homozygotes have no defect in target cell killing, and in vitro RAH GrB and wild type GrB kill cells equally well in the presence of perforin. We conclude that the RAH allele represents a neutral polymorphism in the GrB ge

PMID: 14752093 [PubMed - as supplied by publisher]