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.
Uren
A G
AG
Genentech Inc., South San Francisco, California 94080, USA.
O'Rourke
K
K
Aravind
L A
LA
Pisabarro
M T
MT
Seshagiri
S
S
Koonin
E V
EV
Dixit
V M
VM
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
D011994:Recombinant Proteins; D020169:Caspases