Abstract

Tankyrases are members of the poly (ADP-ribose) polymerases (PARPs). PARPs catalyze the linkage of ADP-ribose onto their substrates either as monomers or polymers using NAD+ as a source. Tankyrase is found in both the cytosol and nuclear compartments and is implicated in many important cellular functions ranging from telomere homeostasis and mitosis to vesicle trafficking (Cong et al., 2011). In mammals, the tankyrase protein family consists of tankyrase 1 and 2, which share 85% amino acid sequence identity. Tankyrases seem only be present in the metazoa (multicellular animals). The tissue expression of the tankyrases varies; TNKS is relatively abundant in reproductive tissues whereas the TNKS2 is more ubiquitous. Tankyrase1 contains four distinct domains. The N-terminus contains the natively disordered HPS domain, followed by a long ankyrin repeat region. This region is clustered into five well conserved subdomains of three ANK repeats each, designated as ARC (ANK repeat cluster) 1-V. Each ARC domain is able to act as an independent unit and can interact with a variety of substrates possessing the sequence region known as the tankyrase binding motif. The SAM (sterile alpha motif) domain contributes to the multimerization of tankyrase 1. The C-terminal region encompasses the PARP domain, which catalyses poly-ADP-ribosylation of acceptor proteins using NAD+ as a substrate (Seimiya et al., 2006). Tankyrase 2 has a similar modular organization as tankyrase1 but lacks the natively disordered HPS domain. Both tankyrases use the ankyrin modules to dock their substrates via their tankyrase binding motif. This motif consists of a minimum of six consecutive amino acids RxxPDG, where only the R and G are always conserved (Guettler et al., 2011). Protein PARsylation can affect the fate of the protein through several ways including direct modulation of its activity, recruitment of binding partners that recognize poly(ADP-ribose) or by affecting protein turn over. Recent studies have shown that the mutation in the TNKS-binding motif of 3BP2 disrupts the interaction with Tankyrase and leads to cherubism in humans.