期刊
FRONTIERS IN BIOSCIENCE-LANDMARK
卷 20, 期 -, 页码 389-404出版社
FRONTIERS IN BIOSCIENCE INC
DOI: 10.2741/4315
关键词
mono-ADP-ribosylation; Toxins; Brefeldin A; PARPs; Immune Response; Cell Survival; Stress; Review
资金
- Italian Association for Cancer Research (AIRC) [IG10341, IG14675]
- PON project [01/00117]
- MIUR Project
- PNR-CNR Aging Program
- FIRC (Italian Foundation for Cancer Research)
The ADP-ribosylation of proteins is a phylogenetically ancient mechanism that involves the transfer of ADP-ribose from nicotinamide adenine dinucleotide (NAD+) to specific amino acids of target proteins post-translationally. In the first part of this review, we briefly describe ADP-ribosylation as the mechanism of action of toxins, while giving particular emphasis to a non-conventional ADP-ribosylation reaction that is mediated by the fungal toxin brefeldin A (BFA). This modification results in the loss of the membrane fission activity of the C-terminal binding protein (CtBP) 1/BFA-ADP-ribosylated substrate (BARS), thus blocking progression of cells into mitosis, with important implications for the design of new anticancer drugs. In addition, we summarize the most recent findings on mammalian, intracellular mono-ADP-ribosyl transferase enzymes, underlining the emerging functional roles in which they are involved, including immune responses, transcriptional regulation, stress responses, cell survival. The observation that several mono-ADP-ribosyl transferases, such as PARP-10, PARP-12, PARP-13, are involved in a range of physiological processes points at the multifunctional feature of these proteins.
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