Báo cáo khoa học: Physiological relevance of the endogenous mono(ADP-ribosyl)ation of cellular proteins

Physiological Relevance of the Endogenous Mono(ADP-ribosyl)ation of Cellular Proteins

Tác giả: Maria Di Girolamo, Nadia Dani, Annalisa Stilla and Daniela Corda

Lĩnh vực: Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy

Nội dung tài liệu: Bài đánh giá này tập trung vào vai trò sinh lý của quá trình mono(ADP-ribosyl)ation nội sinh trong các protein tế bào. Quá trình này, được xúc tác bởi các enzyme ADP-ribosyltransferase (ARTs), bao gồm việc chuyển một gốc ADP-ribose từ βNAD+ sang các protein đích, dẫn đến những thay đổi trong chức năng của chúng. Bài viết khám phá cả các phản ứng ngoại bào và nội bào, làm nổi bật các enzyme liên quan, các protein nền và tác động của chúng đối với các quá trình tế bào như tín hiệu tế bào, trao đổi chất, phản ứng miễn dịch và bệnh lý.

Mục lục chi tiết:

• MINIREVIEW
• Physiological relevance of the endogenous mono(ADP-ribosyl)ation of cellular proteins
• Keywords
• Correspondence
• Abstract
• Enzyme-modulated mono(ADP-ribosyl)ation was originally identified as the mechanism of action of several of the bacterial toxins [1].
• More recently, a series of enzymes that are related to these toxins have been identified in cells, and their potential physiological roles have been explored ([5,6] and references therein; Table 1).
• The mono(ADP-ribosyl)ation reaction is a post-translational modification that is catalysed by both bacterial toxins and eukaryotic enzymes, and that results in the transfer of ADP-ribose from βNAD+ to various acceptor proteins.
• Abbreviations
• Table 1. Mammalian ARTs. See text for details and relevant references.
• that catalysed by the poly(ADP-ribose) polymerases (PARPs; EC 2.4.2.30), which instead transfer branched polymers of ADP-ribose to their target proteins, via an O-glycosidic bond (reviewed in [7a]).
• The mammalian ecto-ADP-ribosyl-transferases (ARTs)
• The mammalian ARTs are coded for by a family of structurally and functionally related genes.
• Despite the low similarity at the amino-acid sequences, there are common structural features that characterize this family of mammalian ARTs [15,16].
• The ecto-ARTs: expression and function
• ART1 is predominantly expressed in skeletal muscle, heart and lung, and in neutrophils and T-cell lymphoma cells [27,28].
• Of note, the human defensin HNP-1 is among the most recently identified substrates of ART1 [30].
• Thus ART1 has been shown to modify HNP-1 on R14 in an in vitro assay [30].
• The ADP-ribosylation reaction as a potential new drug target
• A lack of ART2 expression has been correlated with an enhanced sensitivity to autoimmune disease in several animal models [40,67].
• All of the data discussed above are consistent with the hypothesis that NAD-induced cell death via the activation of the P2X7 receptor has a role in immune responses.
• Other mechanisms that can benefit from ADP-ribosylation-related drugs have emerged from a number of recent reports.
• Intracellular mono(ADP-ribosyl)transferases and endogenous substrates
• Although the ARTs that are able to modify extracellular proteins are the only well characterized family, mono(ADP-ribosyl)ation has also been demonstrated for intracellular proteins involved in cell signalling and metabolism (Table 1; [6] and references therein).
• The same scenario could occur for the two families of mammalian ADP-ribosyltransferases: the ecto-ARTs and the endo-ARTs.
• Fig. 1. (A) Schematic representation of the mammalian mono (ADP-ribosyl)ation reactions.
• The ADP-ribosylation reaction as a potential new drug target
• Acknowledgements
• References