Document Detail


The role of IAP antagonist proteins in the core apoptosis pathway of the mosquito disease vector Aedes aegypti.
MedLine Citation:
PMID:  21274634     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
While apoptosis regulation has been studied extensively in Drosophila melanogaster, similar studies in other insects, including disease vectors, lag far behind. In D. melanogaster, the inhibitor of apoptosis (IAP) protein DIAP1 is the major negative regulator of caspases, while IAP antagonists induce apoptosis, in part, by binding to DIAP1 and inhibiting its ability to regulate caspases. In this study, we characterized the roles of two IAP antagonists, Michelob_x (Mx) and IMP, in apoptosis in the yellow fever mosquito Aedes aegypti. Overexpression of Mx or IMP caused apoptosis in A. aegypti Aag2 cells, while silencing expression of mx or imp attenuated apoptosis. Addition of recombinant Mx or IMP, but not cytochrome c, to Aag2 cytosolic extract caused caspase activation. Consistent with this finding, AeIAP1 bound and inhibited both initiator and effector caspases from A. aegypti, and Mx and IMP competed with caspases for binding to AeIAP1. However, a difference was observed in the BIR domains responsible for Dronc binding by AeIAP1 versus DIAP1. These findings demonstrate that the mechanisms by which IAP antagonists regulate apoptosis are largely conserved between A. aegypti and D. melanogaster, although subtle differences exist.
Authors:
Hua Wang; Rollie J Clem
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Apoptosis : an international journal on programmed cell death     Volume:  16     ISSN:  1573-675X     ISO Abbreviation:  Apoptosis     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-02-25     Completed Date:  2011-08-01     Revised Date:  2012-03-07    
Medline Journal Info:
Nlm Unique ID:  9712129     Medline TA:  Apoptosis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  235-48     Citation Subset:  IM    
Affiliation:
Molecular, Cellular, and Developmental Biology Program, Arthropod Genomics Center, Division of Biology, Kansas State University, Manhattan, KS 66506, USA.
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MeSH Terms
Descriptor/Qualifier:
Aedes / cytology*,  drug effects,  enzymology,  metabolism*
Animals
Apoptosis* / drug effects
Caspases / antagonists & inhibitors,  metabolism
Cell Extracts
Cell Line
Cytochromes c / metabolism
Enzyme Activation / drug effects
Enzyme Inhibitors / pharmacology
Gene Silencing / drug effects
Inhibitor of Apoptosis Proteins / antagonists & inhibitors*,  metabolism
Insect Proteins / metabolism*
Insect Vectors / cytology,  drug effects,  enzymology,  metabolism
Protein Binding / drug effects
Signal Transduction* / drug effects
Sindbis Virus / drug effects,  metabolism
Yellow Fever / parasitology*
Grant Support
ID/Acronym/Agency:
P20 RR16475/RR/NCRR NIH HHS; R21 AI067642/AI/NIAID NIH HHS; R21 AI067642-02/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Cell Extracts; 0/Enzyme Inhibitors; 0/Inhibitor of Apoptosis Proteins; 0/Insect Proteins; 9007-43-6/Cytochromes c; EC 3.4.22.-/Caspases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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