Mono-ADP-ribosylation by PARP10 and PARP14 in genome stability

Abstract

ADP-ribosylation is a post-translational modification involved in a variety of processes including DNA damage repair, transcriptional regulation, and cellular proliferation. Depending on the number of ADP moieties transferred to target proteins, ADP-ribosylation can be classified either as mono-ADP-ribosylation (MARylation) or poly-ADP-ribosylation (PARylation). This post-translational modification is catalyzed by enzymes known as ADP-ribosyltransferases (ARTs), which include the poly (ADP-ribose)-polymerase (PARP) superfamily of proteins. Certain members of the PARP family including PARP1 and PARP2 have been extensively studied and assessed as therapeutic targets. However, the other members of the PARP family of protein are not as well studied but have gained attention in recent years given findings suggesting their roles in an increasing number of cellular processes. Among these other members are PARP10 and PARP14, which have gradually emerged as key players in maintenance of genomic stability and carcinogenesis. PARP10 and PARP14 catalyze the transfer of a single ADP moiety to target proteins. Here, we summarize the current knowledge on MARylation in DNA repair and cancer, focusing on PARP10 and PARP14. We highlight the roles of PARP10 and PARP14 in cancer progression and response to chemotherapeutics and briefly discuss currently known PARP10 and PARP14 inhibitors.

PARP14 is a writer, reader, and eraser of mono-ADP-ribosylation

“…PARP14 was first described as B-cell aggressive lymphoma protein-2 (BAL2), along with PARP9/BAL1 and PARP15/BAL3, as frequently overexpressed in fatal high-risk lymphoma ( 18 , 19 ). PARP14 is involved in multiple signaling pathways linked to cancer, inflammation, and infection ( 20 , 21 , 22 , 23 ), and pharmacological modulation of PARP14 activities may prove as a suitable therapeutic strategy. In all mammals, PARP14 is a >1800-residue multidomain protein.…”

ADP-ribosylation from molecular mechanisms to therapeutic implications

“…PARP7, PARP9, PARP10, and PARP14 have been reported to localize to the nucleus under certain conditions and could contribute to transcription, cell cycle regulation, and genome stability maintenance, including replication fork stability, as recently reviewed. 142 , 143 PARP10, in particular, has been implicated in regulating nuclear factor κB (NF-κB) signaling 144 and cell cycle regulation. 145 , 146 , 147 PARP11 is primarily located at nuclear pores and plays a role in maintaining nuclear envelope stability and remodeling by MARylating several nuclear pore complex proteins.…”

A PARP14/TARG1-Regulated RACK1 MARylation Cycle Drives Stress Granule Dynamics in Ovarian Cancer Cells

“…2). PARP14 is a macrodomain-containing MART that has been implicated in stress responses and cancer (Dhoonmoon and Nicolae, 2023;Dukic et al, 2023;Torretta et al, 2023).…”