C12orf48, termed PARP-1 binding protein, enhances poly(ADP-ribose) polymerase-1 (PARP-1) activity and protects pancreatic cancer cells from DNA damage

Lianhua Piao, Hidewaki Nakagawa, Koji Ueda, Suyoun Chung, Kotoe Kashiwaya, Hidetoshi Eguchi, Hiroaki Ohigashi, Osamu Ishikawa, Yataro Daigo, Koichi Matsuda, Yusuke Nakamura

研究成果: Contribution to journalArticle査読

28 被引用数 (Scopus)

抄録

To identify novel therapeutic targets for aggressive and therapy-resistant pancreatic cancer, we had previously performed expression profile analysis of pancreatic cancers using microarrays and found dozens of genes trans-activated in pancreatic ductal adenocarcinoma (PDAC) cells. Among them, this study focused on the characterization of a novel gene C12orf48 whose overexpression in PDAC cells was validated by Northern blot and immunohistochemical analysis. Its overexpression was observed in other aggressive and therapy-resistant malignancies as well. Knockdown of C12orf48 by siRNA in PDAC cells significantly suppressed their growth. Importantly, we demonstrated that C12orf48 protein could directly interact with Poly(ADP-ribose) Polymerase-1 (PARP-1), one of the essential proteins in the repair of DNA damage, and positively regulate the poly(ADP-ribosyl)ation activity of PARP-1. Depletion of C12orf48 sensitized PDAC cells to agents causing DNA damage and also enhanced DNA damage-induced G2/M arrest through reduction of PARP-1 enzymatic activities. Hence, our findings implicate C12orf48, termed PARP-1 binding protein (PARPBP), or its interaction with PARP-1 to be a potential molecular target for development of selective therapy for pancreatic cancer.

本文言語英語
ページ(範囲)13-24
ページ数12
ジャーナルGenes Chromosomes and Cancer
50
1
DOI
出版ステータス出版済み - 1 2011

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cancer Research

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