PARP16/ARTD15 Is a Novel Endoplasmic-Reticulum-Associated Mono-ADP-Ribosyltransferase That Interacts with, and Modifies Karyopherin-ß1

摘要: Background: Protein mono-ADP-ribosylation is a reversible post-translational modification that modulates the function of target proteins. The enzymes catalyze this reaction in mammalian cells are either bacterial pathogenic toxins or endogenous cellular ADP-ribosyltransferases. latter include members three different families proteins: well characterized arginine-specific ecto-enzymes ARTCs, two sirtuins and, more recently, novel poly(ADP-ribose) polymerase (PARP/ARTD) family have been suggested to act as mono-ADP-ribosyltransferases. Here, we report on characterisation human ARTD15, only known ARTD member with putative C-terminal transmembrane domain. Methodology/Principal Findings: Immunofluorescence and electron microscopy were performed characterise sub-cellular localisation which was found be associated membranes nuclear envelope endoplasmic reticulum. orientation ARTD15 determined using protease protection assay, shown tail-anchored protein cytosolic catalytic Importantly, by combining immunoprecipitation mass spectrometry cell lysates from over-expressing FLAG-ARTD15, identified karyopherin-s1, component trafficking machinery, molecular partner ARTD15. Finally, demonstrate mono-ADP-ribosyltransferase able induce ADP-ribosylation thus defining first substrate for enzyme. Conclusions/Significance: Our data reveal ADP-ribosyltransferase enzyme new intracellular location. identification karyopherin-s1 ARTD15-mediated ADP-ribosylation, hints at regulatory mechanism functions.