Protein mono-ADP-ribosyltransferase PARP10 (PARP10)

Protein mono-ADP-ribosyltransferase PARP10 (PARP10), also known as ARTD10, is a member of the diphtheria toxin-like ADP-ribosyltransferase family that specifically catalyzes the transfer of a single ADP-ribose unit from NAD+ to substrate proteins, a process known as mono-ADP-ribosylation (MARylation) [1, 2, 6]. Unlike the well-known PARP1 and PARP2 enzymes which form long poly-ADP-ribose chains, PARP10 modifies target residues such as glutamate, aspartate, and lysine to regulate protein function and protein-protein interactions [2, 11, 23]. It is a multifunctional protein localized in both the nucleus and cytoplasm, where it interacts with key partners like the proto-oncoprotein c-Myc and the replication factor proliferating cell nuclear antigen (PCNA) [4, 15, 17]. PARP10 is essential for maintaining genomic integrity by facilitating translesion DNA synthesis and the restart of stalled replication forks, thereby helping cells tolerate DNA damage and replication stress [15, 19]. In the context of disease, PARP10 is frequently overexpressed in various human cancers and is considered an oncogene that promotes cellular transformation and tumor growth [15, 21, 23]. Its ability to alleviate replication stress makes it an attractive therapeutic target, as its inhibition can sensitize cancer cells to chemotherapy and radiation [3, 5, 10]. Beyond oncology, PARP10 is involved in regulating the NF-kappaB signaling pathway, mitochondrial metabolism, and innate immune responses, suggesting potential roles in inflammatory and metabolic diseases [6, 9, 15, 23]. While clinical PARP inhibitors primarily target PARP1/2, selective PARP10 inhibitors like OUL35 have been developed as chemical tools and potential drug candidates to exploit the specific vulnerabilities of PARP10-dependent tumors [6, 22]. However, the high conservation of the NAD+ binding pocket across the PARP family presents a significant challenge for achieving the necessary selectivity to avoid off-target toxicities [6, 10, 12].

Other names

ARTD10Poly [ADP-ribose] polymerase 10PARP-10ADP-ribosyltransferase diphtheria toxin-like 10FLJ14464

Inhibition of mono-ADP-ribosyltransferase activity, which prevents the mono-ADP-ribosylation of target proteins involved in DNA repair and cell cycle progression [3, 6, 21].