Mono-ADP-ribosylation: a tool for modulating immune response and cell signaling.
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 Arg(14) 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.
Corda
Daniela
D
Department of Cell Biology and Oncology, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Via Nazionale, 66030 Santa Maria Imbaro, Chieti, Italy. corda@negrisud.it
Di Girolamo
Maria
M
D036002:ADP Ribose Transferases / Q000378:metabolism* / Q000502:physiology; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000818:Animals; D006801:Humans; D007107:Immune System / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology*
D000246:Adenosine Diphosphate Ribose; D036002:ADP Ribose Transferases