title: Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma.
abstract: 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.
authors.affiliation: Genentech Inc., South San Francisco, California 94080, USA.
authors.forename: A G
authors.initials: AG
authors.lastname: Uren
authors.forename: K
authors.initials: K
authors.lastname: O'Rourke
authors.forename: L A
authors.initials: LA
authors.lastname: Aravind
authors.forename: M T
authors.initials: MT
authors.lastname: Pisabarro
authors.forename: S
authors.initials: S
authors.lastname: Seshagiri
authors.forename: E V
authors.initials: EV
authors.lastname: Koonin
authors.forename: V M
authors.initials: VM
authors.lastname: Dixit
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020169:Caspases / Q000737:chemistry / Q000235:genetics*; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D002883:Chromosomes, Human, Pair 14; D003001:Cloning, Molecular; D004023:Dictyostelium / Q000201:enzymology / Q000235:genetics; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000201:enzymology* / Q000235:genetics*; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014162:Transfection; D014178:Translocation, Genetic; D016335:Zinc Fingers
chemical_list: D011994:Recombinant Proteins; D020169:Caspases