Mono-ADP-ribosylation: a tool for modulating immune response and cell signaling

D Corda, M Di Girolamo - Science's STKE, 2002 - science.org
D Corda, M Di Girolamo
Science's STKE, 2002science.org
Mono-ADP-ribosylation is a posttranslational modification of cellular proteins that has the
potential to regulate various cell functions. This reaction consists of the enzymatic transfer of
ADP-ribose to specific acceptor amino acid residues (predominantly arginine and cysteine).
The best-known cellular ADP-ribosyltransferases (the enzymes that catalyze this reaction)
are the seven ectoenzymes, members of the ART family. Recently, ADP-ribosylated human
neutrophil-derived peptide (HNP-1, an antimicrobial peptide secreted by immune cells) has …
Mono-ADP-ribosylation is a posttranslational modification of cellular proteins that has the potential to regulate various cell functions. This reaction consists of the enzymatic transfer of ADP-ribose to specific acceptor amino acid residues (predominantly arginine and cysteine). The best-known cellular ADP-ribosyltransferases (the enzymes that catalyze this reaction) are the seven ectoenzymes, members of the ART family.
Recently, ADP-ribosylated human neutrophil-derived peptide (HNP-1, an antimicrobial peptide secreted by immune cells) has been identified in the bronchoalveolar lavage fluid from individuals who smoke cigarettes. This demonstrates that ADP-ribosylation of HNP-1 occurs in vivo. In vitro experiments have indicated that ART-1, an enzyme also present in the airway epithelium, specifically modifies Arg14 of the HNP-1, causing the loss of the peptide's antimicrobial and cytotoxic activity, while preserving its chemotactic activity. From a functional point of view, these data support a role of ADP-ribosylation in the innate immune response.
Additional functions proposed for the ADP-ribosylation reaction involve the intracellular ADP-ribosyltransferases, which are molecularly unrelated to the ARTs and intervene in cell signaling and metabolism cascades. The growing understanding of the biological roles of protein and peptide ADP-ribosylation represents a powerful tool for novel pharmacological interventions.
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