TY - JOUR
T1 - A caspase-like decoy molecule enhances the activity of a paralogous caspase in the yellow fever mosquito, Aedes aegypti
AU - Bryant, Bart
AU - Ungerer, Mark C.
AU - Liu, Qingzhen
AU - Waterhouse, Robert M.
AU - Clem, Rollie J.
N1 - Funding Information:
We thank Samantha Hartin for construction of pHSP70PLVI+ CASPS18 -epi. This work was supported by NIH grants R21 AI067642 (to R.J.C.) and P20 RR16475 from the BRIN program of the National Center for Research Resources, by the Terry C. Johnson Center for Basic Cancer Research , and by the Kansas Agricultural Experiment Station . R.M.W. was supported by a Wellcome Trust Ph.D. fellowship. This is contribution number 09-283-J from the Kansas Agricultural Experiment Station .
PY - 2010/7
Y1 - 2010/7
N2 - Caspases are cysteine proteases that play critical roles in apoptosis and other key cellular processes. A mechanism of caspase regulation that has been described in mammals and nematodes involves caspase-like decoy molecules, enzymatically inactive caspase homologs that have arisen by gene duplication and acquired the ability to regulate other caspases. Caspase-like decoy molecules are not found in Drosophila melanogaster, raising the question of whether this type of caspase regulation exists in insects. Phylogenomic analysis of caspase genes from twelve Drosophila and three mosquito species revealed several examples of duplicated caspase homologs lacking critical catalytic residues, making them candidate caspase-like decoy molecules. One of these, CASPS18 from the mosquito Aedes aegypti, is a homolog of the D. melanogaster caspase Decay and contains substitutions in two critical amino acid positions, including the catalytic cysteine residue. As expected, CASPS18 lacked caspase activity, but co-expression of CASPS18 with a paralogous caspase, CASPS19, in mosquito cells or co-incubation of CASPS18 and CASPS19 recombinant proteins resulted in greatly enhanced CASPS19 activity. The discovery of potential caspase-like decoy molecules in several insect species opens new avenues for investigating caspase regulation in insects, particularly in disease vectors such as mosquitoes.
AB - Caspases are cysteine proteases that play critical roles in apoptosis and other key cellular processes. A mechanism of caspase regulation that has been described in mammals and nematodes involves caspase-like decoy molecules, enzymatically inactive caspase homologs that have arisen by gene duplication and acquired the ability to regulate other caspases. Caspase-like decoy molecules are not found in Drosophila melanogaster, raising the question of whether this type of caspase regulation exists in insects. Phylogenomic analysis of caspase genes from twelve Drosophila and three mosquito species revealed several examples of duplicated caspase homologs lacking critical catalytic residues, making them candidate caspase-like decoy molecules. One of these, CASPS18 from the mosquito Aedes aegypti, is a homolog of the D. melanogaster caspase Decay and contains substitutions in two critical amino acid positions, including the catalytic cysteine residue. As expected, CASPS18 lacked caspase activity, but co-expression of CASPS18 with a paralogous caspase, CASPS19, in mosquito cells or co-incubation of CASPS18 and CASPS19 recombinant proteins resulted in greatly enhanced CASPS19 activity. The discovery of potential caspase-like decoy molecules in several insect species opens new avenues for investigating caspase regulation in insects, particularly in disease vectors such as mosquitoes.
KW - Apoptosis
KW - Drosophila
KW - Insect
KW - Phylogenetic analysis
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U2 - 10.1016/j.ibmb.2010.04.011
DO - 10.1016/j.ibmb.2010.04.011
M3 - Article
C2 - 20417712
AN - SCOPUS:77953958241
SN - 0965-1748
VL - 40
SP - 516
EP - 523
JO - Insect Biochemistry and Molecular Biology
JF - Insect Biochemistry and Molecular Biology
IS - 7
ER -