Poly [ADP-ribose] polymerase 5A (Tankyrase-1) (TNKS1)

Poly [ADP-ribose] polymerase 5A (PARP-5A), more commonly known as Tankyrase-1 (TNKS1), is a member of the PARP enzyme family that facilitates the transfer of ADP-ribose units onto target proteins (UniProt P54270). It plays a pivotal role in the Wnt/beta-catenin signaling pathway by poly-ADP-ribosylating Axin, which marks it for degradation and allows beta-catenin to accumulate and drive gene expression (PubMed: 19759537). Additionally, TNKS1 regulates telomere length by modifying the telomeric protein TRF1, thereby facilitating telomerase access to telomeres (PubMed: 9732877). In oncology, TNKS1 is a high-priority target because its inhibition can suppress the growth of Wnt-dependent tumors, such as colorectal cancer, by stabilizing Axin and promoting beta-catenin degradation (PubMed: 24213477). Beyond cancer, it is involved in GLUT4 vesicle trafficking and mitotic spindle organization (PubMed: 11533236). Small-molecule inhibitors like XAV939 and G007-LK have been developed to target its catalytic domain, though clinical progression faces challenges regarding intestinal toxicity due to the target's role in normal tissue homeostasis (PubMed: 23644361).

Other names

Tankyrase-1TNKSTNKS1PARP5APARPLTIN1TINF1TRF1-interacting ankyrin-related ADP-ribose polymerase

Inhibition of the catalytic PARP domain to prevent the poly-ADP-ribosylation of Axin, which stabilizes Axin and promotes the degradation of beta-catenin, thereby inhibiting oncogenic Wnt signaling.