Gu Kang Bong, Kang Sung-Ung, Jin Kim Jae, Kwon Ji-Sun, Gagné Jean-Philippe, Yun Lee Seo, Kim Soyeon, Lee Karl S, Ha Shinwon, Seop Jeong Jun, Lee Yun-Il, Zhu Heng, Kim Dongsan, Poirier Guy G, Chul Kang Ho, Dawson Valina L, Dawson Ted M
Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States.
Nucleic Acids Res. 2025 Apr 10;53(7). doi: 10.1093/nar/gkaf300.
Poly (ADP-ribose) (PAR) plays a crucial role in intracellular signaling and scaffolding through covalent modification or non-covalent binding to target proteins. The non-covalent PAR binding proteome (PARylome) has not been extensively characterized. Here we performed a PAR-binding screen using a human protein microarray that covers most of the human proteome to characterize the non-covalent binding PARylome. A total of 356 PAR-binding proteins were identified. The PAR-binding PARylome suggests that PAR binding regulates a variety of biological processes beyond DNA damage signaling and DNA repair. Proteins that may be reprogrammed by PAR binding include signaling molecules, transcription factors, nucleic acid binding proteins, calcium binding proteins, ligases, oxidoreductases, enzymes, transferases, hydrolases, and receptors. The global database of PAR-binding proteins that we established will be a valuable tool for further in-depth analysis of the role of PARylation in a wide range of biological contexts.
聚（ADP-核糖）（PAR）通过与靶蛋白的共价修饰或非共价结合，在细胞内信号传导和支架形成中发挥关键作用。非共价PAR结合蛋白质组（PARylome）尚未得到广泛表征。在这里，我们使用覆盖大部分人类蛋白质组的人类蛋白质微阵列进行了PAR结合筛选，以表征非共价结合的PARylome。共鉴定出356种PAR结合蛋白。PAR结合的PARylome表明，PAR结合除了调节DNA损伤信号传导和DNA修复之外，还调控多种生物学过程。可能通过PAR结合进行重编程的蛋白质包括信号分子、转录因子、核酸结合蛋白、钙结合蛋白、连接酶、氧化还原酶、酶、转移酶、水解酶和受体。我们建立的PAR结合蛋白全局数据库将成为进一步深入分析PARylation在广泛生物学背景中作用的宝贵工具。
