title: Functional characterization of the poly(ADP-ribose) polymerase activity of tankyrase 1, a potential regulator of telomere length.
abstract: Poly(ADP-ribose) polymerases (PARPs) comprise a growing family of enzymes known to be involved in genotoxic signaling and metabolic regulation. One of the latest family members, tankyrase 1, was shown to be involved in maintenance of telomere integrity. Here we expressed full-length tankyrase 1 and a fragment, termed T-PARP, spanning the poly(ADP-ribose) polymerase domain and characterized the enzymatic properties of the two proteins. Both, tankyrase 1 and T-PARP catalyze an auto poly(ADP-ribosyl)ation reaction with comparable catalytic activity. In contrast, (ADP-ribosyl)ation of TRF1, a previously described substrate, is strongly performed only by the full-length enzyme but not by T-PARP. Characterization of the poly(ADP-ribose) products reveals that tankyrase 1 synthesizes polymers with an average chain length of 20 units and no detectable branching of the polymers. Finally, we show that the catalytic efficiency of tankyrase 1, as expressed by the k(cat)/K(m) value, is approximately 150-fold lower compared to the basal activity of the poly(ADP-ribose) polymerase, PARP 1.
authors.affiliation: Department of Oncology Research, Boehringer Ingelheim Pharma KG, Birkendorfer Strasse 65, 88397, Biberach, Germany.
authors.forename: Jörg F
authors.initials: JF
authors.lastname: Rippmann
authors.forename: Klaus
authors.initials: K
authors.lastname: Damm
authors.forename: Andreas
authors.initials: A
authors.lastname: Schnapp
mesh_terms: D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D038501:Tankyrases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism*; D035321:Telomeric Repeat Binding Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009243:NAD; D010446:Peptide Fragments; D011994:Recombinant Proteins; D038501:Tankyrases; D035321:Telomeric Repeat Binding Protein 1; C418109:TNKS protein, human