Poly(ADP-ribose) polymerase family members (PARP family)

The "Other PARP family members" refers to the group of enzymes within the poly(ADP-ribose) polymerase family, excluding the well-characterized PARP1 and PARP2. This group includes PARP3, Vault PARP (PARP4), Tankyrases (TNKS1 and TNKS2), and several mono-ADP-ribosyltransferases (PARP6-16) (Lüscher et al., 2022). While PARP1 and PARP2 are the primary targets for clinically approved PARP inhibitors used in DNA repair-deficient cancers, these other family members perform diverse biological roles including telomere maintenance, Wnt signaling regulation, and immune response modulation (Morales et al., 2014). For instance, Tankyrases are critical regulators of the Wnt/beta-catenin pathway, making them attractive targets for colorectal cancer, while PARP7 has emerged as a key regulator of the type I interferon response in the tumor microenvironment (Goenka and Bidere, 2020). Emerging therapeutic strategies focus on developing isoform-specific inhibitors to target these unique functions while avoiding the broad myelosuppression associated with pan-PARP inhibition (Mariotti et al., 2020). Consequently, these other PARPs represent a significant frontier in precision oncology and immunology (Vyas et al., 2013).

Other names

PARP3PARP4Tankyrase 1Tankyrase 2PARP6PARP7PARP8PARP9PARP10PARP11PARP12PARP13PARP14PARP15PARP16ARTD family

Inhibition of catalytic ADP-ribosyltransferase activity (poly- or mono-ADP-ribosylation), leading to the modulation of specific cellular pathways such as DNA repair (PARP3), Wnt/beta-catenin signaling (Tankyrases), or the innate immune response (PARP7).