Identification and characterization of murine caspase-14, a new member of the caspase family.
We report here the identification and characterization of a new member of the mouse caspase family, named caspase-14. Northern blot analysis of mRNA from various tissues with caspase-14-specific probe showed a major transcript size of approximately 2.4 kb and variant transcripts of 2.0 kb and 1.5 kb. The major transcript is detected mainly in the liver and to a lesser extent in the brain and kidney. Caspase-14 cDNA encodes a 257-amino acid-long protein that has significant homology to other members of the caspase family. Like other caspases, caspase-14 has a conserved active site, pentapeptide QACRG. However, it lacks an NH2-terminal prodomain or a caspase recruitment domain, suggesting that it could be a downstream caspase that depends on other initiator caspases for activation. Consistent with this, procaspase-14 can be processed in vitro by the death receptor-associated caspase-8 and caspase-10 but not other caspases, and in vivo after stimulation of cells with anti-Fas agonist antibody or Tumor Necrosis Factor-Related Apoptosis Inducing Ligand. Furthermore, procaspase-14 can be cleaved by granzyme B. These observations suggest that caspase-14 may play a role in death receptor and granzyme B-induced apoptosis.
Ahmad
M
M
Center for Apoptosis Research, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Srinivasula
S M
SM
Hegde
R
R
Mukattash
R
R
Fernandes-Alnemri
T
T
Alnemri
E S
ES
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D018076:DNA, Complementary / Q000032:analysis; D004792:Enzyme Precursors / Q000378:metabolism; D053804:Granzymes; D051379:Mice; D008969:Molecular Sequence Data; D012697:Serine Endopeptidases / Q000378:metabolism; D013379:Substrate Specificity
D018076:DNA, Complementary; D004792:Enzyme Precursors; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases