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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


  • Uren AG
  • O'Rourke K
  • Aravind LA
  • Pisabarro MT
  • Seshagiri S
  • Koonin EV
  • Dixit VM


Molecular cell

Publication Data

October 9, 2000

Associated Grants


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