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Chemical genetic methodologies for identifying protein substrates of PARPs

期刊

TRENDS IN BIOCHEMICAL SCIENCES
卷 47, 期 5, 页码 390-402

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CELL PRESS
DOI: 10.1016/j.tibs.2021.07.002

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  1. NIH [NIH 2R01NS088629]

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In this review, the design principles behind two chemical genetic strategies for identifying direct protein substrates of individual PARP family members are discussed, providing novel insights into the cellular function of individual PARPs and PARP-mediated ADP-ribosylation.
Poly-ADP-ribose-polymerases (PARPs) are a family of 17 enzymes that regulate a diverse range of cellular processes in mammalian cells. PARPs catalyze the acids on protein substrates, in a process known as ADP-ribosylation. Identifying the direct protein substrates of individual PARP family members is an essential first step for elucidating the mechanism by which PARPs regulate a particular pathway in cells. Two distinct chemical genetic (CG) strategies have been developed for identifying the direct protein substrates of individual PARP family members. In this review, we discuss the design principles behind these two strategies and how target identification has provided novel insight into the cellular function of individual PARPs and PARP-mediated ADP-ribosylation.

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