Poly [ADP-ribose] polymerase 1, Poly [ADP-ribose] polymerase 2, Tankyrase-1, and Tankyrase-2 (PARP1, PARP2, TNKS1, TNKS2)

Poly [ADP-ribose] polymerase 1 (PARP1), Poly [ADP-ribose] polymerase 2 (PARP2), Tankyrase-1 (TNKS1), and Tankyrase-2 (TNKS2) are key enzymes within the poly [ADP-ribose] polymerase family that regulate diverse cellular processes through the post-translational modification of proteins [1, 10, 12]. PARP1 and PARP2 are primarily involved in the detection and repair of DNA damage, particularly single-strand breaks, and are the primary targets of clinically approved PARP inhibitors used to treat BRCA-mutated cancers via synthetic lethality [5, 11, 13, 21]. Tankyrase-1 and Tankyrase-2 (also known as PARP5a and PARP5b) are distinct members that regulate the canonical Wnt/beta-catenin signaling pathway by modulating the stability of Axin, a key component of the beta-catenin destruction complex [1, 3, 6, 20]. Beyond DNA repair and Wnt signaling, these enzymes play roles in telomere maintenance, mitotic spindle assembly, and metabolic regulation [5, 6, 8, 14, 16]. Drugs targeting these molecules include pan-PARP inhibitors, tankyrase-selective inhibitors, and dual-action agents like E7449, which target both DNA repair and Wnt signaling pathways [4, 7, 9, 21]. While PARP1/2 inhibition is a validated therapeutic strategy in oncology, the clinical application of tankyrase inhibitors has been limited by on-target toxicities in the gastrointestinal tract and bone [9, 10, 21]. Understanding the overlapping and unique functions of these four enzymes is crucial for developing next-generation therapies with improved selectivity and reduced side effects [1, 10, 16].

Other names

ARTD1ARTD2ARTD5ARTD6PARP5APARP5BTankyrase-1Tankyrase-2Poly [ADP-ribose] polymerase tankyrase-1Poly [ADP-ribose] polymerase tankyrase-2ADPRTPPOL

PARP inhibition, PARP trapping, Synthetic lethality in BRCA-deficient cells, and Wnt/beta-catenin pathway inhibition via Axin stabilization.