Poly(ADP-ribose) polymerase 4, 10, 12, 15, and 16 (PARP4/10/12/15/16)

PARP4, 10, 12, 15, and 16 represent a subset of the poly(ADP-ribose) polymerase (PARP) family, which are enzymes involved in the post-translational modification of proteins via ADP-ribosylation. While PARP4 (Vault PARP) is primarily a poly-ADP-ribosyltransferase, PARP10, 12, 15, and 16 are mono-ADP-ribosyltransferases that transfer a single ADP-ribose unit to substrate proteins. These enzymes play diverse roles in cellular physiology, including the regulation of DNA repair, cell cycle progression, the unfolded protein response (UPR) in the endoplasmic reticulum, and the innate immune response to viral infections. In the context of oncology, these non-canonical PARP members have gained attention as significant off-targets or secondary targets of clinical PARP inhibitors like talazoparib and olaparib. Their inhibition can contribute to the overall polypharmacology and therapeutic efficacy of these drugs, particularly in sensitizing cancer cells to DNA damage and stress-induced apoptosis.

Other names

ARTD4ARTD10ARTD12ARTD7ARTD15Vault PARPpART7BAL3

Competitive inhibition of the NAD+ binding site in the catalytic domain of PARP enzymes, preventing the transfer of ADP-ribose units to target proteins.