Poly(ADP-ribose) polymerase 1, Poly(ADP-ribose) polymerase 2, and Tankyrase (PARP1, PARP2, TNKS)

Poly(ADP-ribose) polymerase 1, poly(ADP-ribose) polymerase 2, and tankyrase are key members of the PARP family of enzymes, which catalyze the transfer of ADP-ribose units to acceptor proteins as part of the cellular response to DNA damage and the regulation of diverse processes, including DNA repair, chromatin remodeling, signal transduction, and cell division[1][3][5][6]. PARP1 and PARP2 are major mediators of DNA single- and double-strand break repair via poly(ADP-ribosyl)ation. Tankyrases (TNKS1, TNKS2) regulate telomere maintenance and Wnt/β-catenin signaling through ADP-ribosylation of target proteins, such as AXIN. Dysregulation or inhibition of these enzymes has profound effects on cell survival, especially in tumor cells deficient in homologous recombination (e.g., BRCA1/2 mutant cancers), and underlies the clinical success of PARP inhibitors for cancer therapy. Tankyrase inhibitors are being investigated for their anti-cancer potential but face challenges in efficacy and safety. These targets are the focus of intense research for pharmacological modulation in oncology and beyond[6][5][3][1].

Other names

ARTD1EC 2.4.2.30poly(ADP-ribose) synthase 1ARTD2Tankyrase 1PARP5aTankyrase 2PARP5b

Inhibition of poly(ADP-ribose) polymerase activity, leading to disruption of DNA damage repair in cancer cells (synthetic lethality in BRCA-mutant cancers). For tankyrase inhibitors: Block ADP-ribosylation of AXIN, resulting in stabilization of AXIN and inhibition of Wnt/β-catenin signaling in tumors. Prevention of chromatin or spindle modifications in dividing cells. AutoPARylation and heteroPARylation regulation.