Overview on poly(ADP-ribose) immuno-biomedicine and future prospects

Abstract

Poly(ADP-ribose), identified in 1966 independently by three groups Strassbourg, Kyoto and Tokyo, is synthesized by poly(ADP-ribose) polymerases (PARP) from NAD+ as a substrate in the presence of Mg2+. The structure was unique in that it has ribose-ribose linkage. In the early-1970s, however, its function in vivo/in vitro was still controversial and the antibody against it was desired to help clear its significance. Thereupon, the author tried to produce antibody against poly(ADP-ribose) in rabbits and succeeded in it for the first time in the world. Eventually, this success has led to the following two groundbreaking papers in Nature: “Naturally-occurring antibody against poly(ADP-ribose) in patients with autoimmune disease SLE”, and “Induction of anti-poly(ADP-ribose) antibody by immunization with synthetic double-stranded RNA, poly(A)·poly(U)”.On the way to the publication of the first paper, a reviewer gave me a friendly comment that there is “heteroclitic” fashion as a mechanism of the production of natural antibody. This comment was really a God-send for me, and became a train of power for publication of another paper, as described above. Accordingly, I thought this, I would say, episode is worth describing herein. Because of its importance in biomedical phenomena, a certain number of articles related to “heteroclitic” have become to be introduced in this review, although they were not always directly related to immuno-biological works on poly(ADP-ribose). Also, I tried to speculate on the future prospects of poly(ADP-ribose), product of PARP, as an immuno-regulatory molecule, including either induced or naturally-occurring antibodies, in view of “heteroclitic”.

Mitochondrial NAD+ Controls Nuclear ARTD1-Induced ADP-Ribosylation

“…MARylation has been described to regulate several important biological processes ( Lüscher et al., 2018 ). Detection of cellular MARylation has remained challenging due to the fact that common anti-ADP-ribosylation antibodies preferentially bind to long PAR chains ( Kanai, 2016 ). While synthesis of chemically ADP-ribosylated peptides for antibody generation has remained challenging ( Voorneveld et al., 2018 ), amine-linked ADP-ribose-modified proteins have been used to successfully generate polyclonal antibodies that recognize MARylated proteins ( Meyer and Hilz, 1986 ).…”

Poly (ADP-ribose) polymerase 1 (PARP1) inhibition promotes pulmonary metastasis of osteosarcoma by boosting ezrin phosphorylation

“…PARPs are also found linked to stress responses, metabolism, and cancer [12]. PARP inhibitors bind to the NAD binding pocket in the catalytic domain of PARPs and hinder the synthesis of PAR [11][12][13]. PARP1 contributes to over 90% of PAR synthesis and is considered as the major target for PARP inhibitors [14].…”

“…Poly (ADP-ribose) polymerases (PARPs) are a family of enzymes regulating DNA repair and genome transcription [11][12][13]. They posttranslationally modify proteins by attaching ADP-ribose polymers (or poly ADP-ribose, PAR) on certain domains using NAD as a substrate, which process is termed as PARylation.…”

PARP-1/2 Inhibitor Olaparib Prevents or Partially Reverts EMT Induced by TGF-β in NMuMG Cells

“…The PAR chains on these target proteins can interact non-covalently with specific protein domains, namely PBZ, WWE, PBM, RRM, and macro-domains. PAR is degraded mainly by poly-(ADP-ribosyl) glycohydrolase (PARG) activity [1,2,3].…”