Caspase 1
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]