PARP9
Description
The PARP9 (poly(ADP-ribose) polymerase family member 9) is a protein-coding gene located on chromosome 3.
PARP9, also known as ADP-ribosyltransferase diphtheria toxin-like 9, B aggressive lymphoma protein, or Poly [ADP-ribose] polymerase 9, is an ADP-ribosyltransferase that forms a complex with the E3 ligase DTX3L. This complex plays a role in DNA damage repair and immune responses, including interferon-mediated antiviral defenses. The complex enhances DTX3L E3 ligase activity, which is further boosted by PARP9 binding to poly(ADP-ribose). In the presence of E1 and E2 enzymes, the complex mediates NAD(+)-dependent mono-ADP-ribosylation of ubiquitin, preventing ubiquitin conjugation to substrates such as histones. During DNA repair, PARP1 recruits the PARP9/BAL1-DTX3L complex to DNA damage sites by binding to ribosylated PARP1. Subsequent PARP1-dependent ubiquitination by the complex promotes the recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to damage sites. The PARP9-DTX3L complex is necessary for efficient non-homologous end joining (NHEJ) in response to DNA damage, and its function is negatively modulated by PARP9 activity. While PARP9 is dispensable for B-cell receptor (BCR) assembly through V(D)J recombination and class switch recombination (CSR), it positively regulates pro-inflammatory cytokine production in macrophages stimulated by IFNG. This regulation is achieved by suppressing PARP14-mediated STAT1 ADP-ribosylation, promoting STAT1 phosphorylation and suppressing PARP14-mediated STAT6 ADP-ribosylation. PARP9 interacts with DTX3L, forming a stable complex that is required for PARP9-mediated ADP-ribosylation of ubiquitin. The interaction between PARP9 and DTX3L occurs through the PARP catalytic domain of PARP9 and the N-terminus of DTX3L. PARP9 also forms complexes with STAT1 and DTX3L, independent of IFNB1 or IFNG-mediated STAT1 'Tyr-701' phosphorylation, and with STAT1, DTX3L, and histone H2B H2BC9/H2BJ, potentially leading to H2BC9/H2BJ ubiquitination. PARP9 interacts with STAT1 through its N-terminus and with PARP14 in IFNG-stimulated macrophages, preventing PARP14-mediated STAT1 and STAT6 ADP-ribosylation. Finally, PARP9 interacts with PARP1 when it is poly-ADP-ribosylated.
PARP9 is also known as ARTD9, BAL, BAL1, MGC:7868.
