Abstract:
PARPs catalyze ADP-ribosylation-a post-translational modification that plays crucial roles in biological processes, including DNA repair, transcription, immune regulation, and condensate formation. ADP-ribosylation can be added to a wide range of amino acids with varying lengths and chemical structures, making it a complex and diverse modification. Despite this complexity, significant progress has been made in developing chemical biology methods to analyze ADP-ribosylated molecules and their binding proteins on a proteome-wide scale. Additionally, high-throughput assays have been developed to measure the activity of enzymes that add or remove ADP-ribosylation, leading to the development of inhibitors and new avenues for therapy. Real-time monitoring of ADP-ribosylation dynamics can be achieved using genetically encoded reporters, and next-generation detection reagents have improved the precision of immunoassays for specific forms of ADP-ribosylation. Further development and refinement of these tools will continue to advance our understanding of the functions and mechanisms of ADP-ribosylation in health and disease.
摘要:
PARP催化ADP-核糖基化-一种在生物过程中起关键作用的翻译后修饰,包括DNA修复,转录,免疫调节,和凝析油形成。ADP-核糖基化可以添加到具有不同长度和化学结构的多种氨基酸中,使它成为一个复杂而多样的修改。尽管复杂,在开发化学生物学方法以在蛋白质组范围内分析ADP-核糖基化分子及其结合蛋白方面取得了重大进展。此外,已经开发了高通量测定法来测量添加或去除ADP-核糖基化的酶的活性,导致抑制剂和新的治疗途径的发展。ADP核糖基化动力学的实时监测可以使用基因编码的报告基因来实现,和下一代检测试剂提高了特定形式ADP-核糖基化免疫测定的精度。这些工具的进一步发展和完善将继续推进我们对健康和疾病中ADP-核糖基化的功能和机制的理解。