Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma.
Caspases are cysteine proteases essential to apoptosis. We have identified two families of caspase-like proteins, Paracaspases (found in metazoans and Dictyostelium) and metacaspases (found in plants, fungi, and protozoa). Metazoan paracaspase prodomains contain a death domain and immunoglobulin domains. Several plant metacaspase prodomains contain zinc finger motifs resembling those in the plant hypersensitive response/cell death protein Isd-1. The human paracaspase prodomain binds Bcl10, a protein involved in the t(1;14)(p22;q32) translocation of mucosa-associated lymphoid tissue (MALT) lymphoma. Another MALT lymphoma translocation, t(11;18)(q21;q21), fuses the IAP-2 gene to the MLT1/MALT1 locus, which encodes the human paracaspase. We find that this fusion activates NF-kappaB and that the caspase domain is required for this function, since mutation of the conserved catalytic cysteine attenuates NF-kappaB activation.
Pubmed ID: 11090634 RIS Download
Amino Acid Sequence | Animals | Caspases | Chromosome Mapping | Chromosomes, Human, Pair 1 | Chromosomes, Human, Pair 14 | Cloning, Molecular | Dictyostelium | Humans | Lymphoma, B-Cell, Marginal Zone | Molecular Sequence Data | Recombinant Proteins | Sequence Alignment | Sequence Homology, Amino Acid | Species Specificity | Transfection | Translocation, Genetic | Zinc Fingers