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Independent Proteolytic Activities Control the Stability and Size of <b><i>Drosophila </i></b>Inhibitor of Apoptosis 2 Protein
Author(s) -
Silvia Guntermann,
Brittany Fraser,
Bart Hazes,
Edan Foley
Publication year - 2015
Publication title -
journal of innate immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.078
H-Index - 64
eISSN - 1662-8128
pISSN - 1662-811X
DOI - 10.1159/000381475
Subject(s) - inhibitor of apoptosis , biology , innate immune system , apoptosis , microbiology and biotechnology , signal transduction , ubiquitin , xiap , caspase , inhibitor of apoptosis domain , immune system , ubiquitin ligase , programmed cell death , immunology , biochemistry , gene
The Drosophila immune deficiency pathway defends many bacterial pathogens and bears striking molecular similarities to the mammalian tumor necrosis factor signal transduction pathway. Orthologous inhibitors of apoptosis ubiquitin ligases act at a proximal stage of both responses to coordinate the assembly of signal transduction platforms that shape host immune responses. Despite the importance of inhibitor of apoptosis proteins within evolutionarily conserved innate immune responses, we know relatively little about the cellular machinery that controls inhibitor of apoptosis activity. In this study, we examined the molecular basis for inhibitor of apoptosis 2 protein regulation in the immune deficiency pathway. Our studies identified two distinct proteolytic events that determine the stability and composition of cellular inhibitor of apoptosis 2 protein pools. We found that apoptotic caspase activity cleaves inhibitor of apoptosis 2 at an N-terminal aspartate to generate a truncated protein that retains the ability to interact with immune deficiency pathway members. We also showed that a C-terminal ubiquitin ligase activity within inhibitor of apoptosis 2 directs the proteasomal destruction of full-length and truncated inhibitor of apoptosis 2 isoforms. These studies add to our appreciation of the regulation of innate immunity and suggest potential links between apoptotic caspases and innate defenses.

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