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J. Biol. Chem., Vol. 276, Issue 27, 25342-25350, July 6, 2001
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From the Caspases are main effectors of apoptosis in
metazoans. Genome analysis indicates that there are seven
caspases in Drosophila, six of which have been previously
characterized. Here we describe the cloning and characterization of the
last Drosophila caspase, DAMM. Similar to mammalian
effector caspases, DAMM lacks a long prodomain. We show that the DAMM
precursor, along with the caspases DRONC and DECAY, is partially
processed in cells undergoing apoptosis. Recombinant DAMM produced in
Escherichia coli shows significant catalytic activity on a
pentapeptide caspase substrate. Low levels of damm mRNA
are ubiquitously expressed in Drosophila embryos during
early stages of development. Relatively high levels of damm mRNA are detected in larval salivary glands and
midgut, and in adult egg chambers. Ectopic expression of DAMM in
cultured cells induces apoptosis, and similarly, transgenic
overexpression of DAMM, but not of a catalytically inactive DAMM
mutant, in Drosophila results in a rough eye
phenotype. We demonstrate that expression of the catalytically
inactive DAMM mutant protein significantly suppresses the rough eye
phenotype due to the overexpression of HID, suggesting that DAMM
may be required in a hid-mediated cell death pathway.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AF240763.
Characterization of the Drosophila
Caspase, DAMM*
§,,,,,
, and**
Hanson Centre for Cancer Research, Institute
of Medical and Veterinary Science, Frome Road, Adelaide, SA 5000, Australia and the ¶ Peter MacCallum Cancer Institute, St.
Andrew's Place, Melbourne, Victoria 8006, Australia
*
This work was supported in part by funds from the Wellcome
Trust, Anti-Cancer Foundation of South Australia, and the National Health and Medical Research Council.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Wellcome Trust Senior Fellow in Medical Science.
**
To whom correspondence should be addressed: Hanson Center
for Cancer Research, IMVS, P.O. Box 14, Rundle Mall, Adelaide, SA 5000, Australia. Tel.: 61-8-8222-3738; Fax: 61-8-8222-3139; E-mail: sharad.kumar@imvs.sa.gov.au.
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