PolyADP-ribosylation and cancer.
The polyADP-ribosylation reaction results in a unique post-translational modification involved in various cellular processes and conditions, including DNA repair, transcriptional control, genomic stability, cell death and transformation. The existence of 17 members of the poly(ADP-ribose) polymerase (PARP) family has so far been documented, with overlapping functional consequences. PARP-1 is known to be involved in DNA base excision repair and this explains the susceptibility spectrum of PARP-1 knockout animals to genotoxic carcinogens. The fact that centrosome amplification is induced by a non-genotoxic inhibitor of PARP and in PARP-1 knockout mouse cells, is in line with aneuploidy, which is frequent in cancers. Genetically engineered animal models have revealed that PARP-1 and VPARP impact carcinogenesis. Furthermore, accumulating experimental evidence supports the utility of PARP and PARG inhibitors in cancer therapy and several clinical trials are now ongoing. Increasing NAD(+) levels by pharmacological supplementation with niacin has also been found to exert preventive effects against cancer. In the present review, recent research progress on polyADP-ribosylation related to neoplasia is summarized and discussed.
Miwa
Masanao
M
Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura-cho Nagahama, Shiga 526-0829, Japan. m_miwa@nagahama-i-bio.ac.jp
Masutani
Mitsuko
M
D000818:Animals; D016923:Cell Death; D042822:Genomic Instability; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*
D011065:Poly(ADP-ribose) Polymerases