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.
Mesh Terms:
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
Mol. Cell
Date: Oct. 01, 2000
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