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Sci. STKE, 17 December 2002
Vol. 2002, Issue 163, p. pe53
[DOI: 10.1126/stke.2002.163.pe53]

PERSPECTIVES

Mono-ADP-Ribosylation: A Tool for Modulating Immune Response and Cell Signaling

Daniela Corda* and Maria Di Girolamo

Department of Cell Biology and Oncology, Istituto di Ricerche Farmacologiche "Mario Negri," Consorzio Mario Negri Sud, Via Nazionale, 66030 Santa Maria Imbaro, Chieti, Italy.

Abstract: 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.

*Corresponding author. E-mail: corda{at}negrisud.it

Citation: D. Corda, M. Di Girolamo, Mono-ADP-Ribosylation: A Tool for Modulating Immune Response and Cell Signaling. Sci. STKE 2002, pe53 (2002).

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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T. Tsurumura, Y. Tsumori, H. Qiu, M. Oda, J. Sakurai, M. Nagahama, and H. Tsuge (2013)
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