Functional Characterization of the Poly(ADP-ribose) Polymerase Activity of Tankyrase 1, a Potential Regulator of Telomere Length

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...

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Bibliographic Details
Published in:Journal of molecular biology 2002-10, Vol.323 (2), p.217-224
Main Authors: Rippmann, Jörg F., Damm, Klaus, Schnapp, Andreas
Format: Article
Language:English
Subjects:
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
enzyme kinetics
Humans
Membrane Proteins - chemistry
Membrane Proteins - genetics
Membrane Proteins - metabolism
NAD
NAD - metabolism
Peptide Fragments - genetics
Peptide Fragments - metabolism
poly(ADP-ribose)
Protein Structure, Tertiary
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
tankyrase
Tankyrases - chemistry
Tankyrases - genetics
Tankyrases - metabolism
Telomere - metabolism
Telomeric Repeat Binding Protein 1 - genetics
Telomeric Repeat Binding Protein 1 - metabolism
TRF1
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Summary: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.
ISSN:0022-2836
1089-8638
DOI:10.1016/S0022-2836(02)00946-4