title: Regulation of nucleocytoplasmic transport by ADP-ribosylation: the emerging role of karyopherin-β1 mono-ADP-ribosylation by ARTD15.
abstract: Post-translational modifications of a cellular protein by mono- and poly-ADP-ribosylation involve the cleavage of NAD (+) , with the release of its nicotinamide moiety. This is accompanied by the transfer of a single (mono-) or several (poly-) ADP-ribose molecules from NAD (+) to a specific amino-acid residue of the protein. Recent reports have shed new light on the correlation between NAD (+) -dependent ADP-ribosylation reactions and the endoplasmic reticulum, in addition to the well-documented roles of these reactions in the nucleus and mitochondria. We have demonstrated that ARTD15/PARP16 is a novel mono-ADP-ribosyltransferase with a new intracellular location, as it is associated with the endoplasmic reticulum. The endoplasmic reticulum, which is a membranous network of interconnected tubules and cisternae, is responsible for specialised cellular functions, including protein folding and protein transport. Maintenance of specialised cellular functions requires the correct flow of information between separate organelles that is made possible through the nucleocytoplasmic trafficking of proteins. ARTD15 appears to have a role in nucleocytoplasmic shuttling, through karyopherin-β1 mono-ADP-ribosylation. This is in line with the emerging role of ADP-ribosylation in the regulation of intracellular trafficking of cellular proteins. Indeed, other, ADP-ribosyltransferases like ARTD1/PARP1, have been reported to regulate nucleocytoplasmic trafficking of crucial proteins, including p53 and NF-κB, and as a consequence, to modulate the subcellular localisation of these proteins under both physiological and pathological conditions.
authors.affiliation: G-Protein-Mediated Signalling Laboratory, Fondazione Mario Negri Sud, Via Nazionale 8/A, 66030, S. Maria Imbaro (CH), Italy, mdigirolamo@negrisud.it.
authors.forename: Maria
authors.initials: M
authors.lastname: Di Girolamo
mesh_terms: D021581:Active Transport, Cell Nucleus; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D006801:Humans; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D028961:beta Karyopherins / Q000235:genetics / Q000378:metabolism*
chemical_list: C424166:KPNB1 protein, human; D028961:beta Karyopherins; D000246:Adenosine Diphosphate Ribose; C576117:PARP16 protein, human; D011065:Poly(ADP-ribose) Polymerases