Tankyrase 1 and tankyrase 2 (TNKS1 and TNKS2)

Tankyrase 1 and tankyrase 2 are closely related enzymes of the poly(ADP-ribose) polymerase (PARP) superfamily, encoded by the TNKS and TNKS2 genes in humans. They catalyze the poly(ADP-ribosyl)ation (PARylation) of target proteins, marking them for ubiquitination and subsequent degradation by the proteasome[3][4]. Their core functions include regulating telomere length (mainly through interaction and PARylation of the telomere-binding protein TRF1), ensuring proper resolution of sister telomere cohesion during mitosis, and activating the Wnt/β-catenin pathway by PARylating AXIN1/2, thus promoting β-catenin signaling[1][2][3]. Tankyrases also interact with multiple cellular partners to control processes such as protein trafficking (e.g., GLUT4), DNA repair, and cell death. Their dysregulation is implicated in tumorigenesis, making them notable targets for cancer therapy, particularly in Wnt-dependent cancers. Multiple small molecule inhibitors of tankyrases have been developed and are under investigation as anti-cancer agents. However, their roles in various normal physiological processes raise concerns about potential side effects and require careful evaluation in therapeutic contexts[4][1][3][6][7].

Other names

Poly(ADP-ribose) polymerase 5a (PARP5a)Poly(ADP-ribose) polymerase 5b (PARP5b)ADP-ribosyltransferase diphtheria toxin-like 5 (ARTD5)ADP-ribosyltransferase diphtheria toxin-like 6 (ARTD6)TNKS (for Tankyrase 1)TNKS2 (for Tankyrase 2)Tankyrase (for either or both, context-dependent)

Tankyrase inhibitors block the poly(ADP-ribosyl)ation (PARylation) activity of tankyrases, preventing ubiquitination and degradation of proteins such as AXIN1 and AXIN2, thereby stabilizing the β-catenin destruction complex to inhibit Wnt/β-catenin signaling[3][4].\nInhibitors prevent PARylation-mediated release of TRF1 from telomeres, impacting telomere maintenance[2][3].