期刊
BIOMOLECULES
卷 3, 期 1, 页码 1-17出版社
MDPI AG
DOI: 10.3390/biom3010001
关键词
Poly(ADP-ribose); PARP; PARG; macrodomain; protein modification
资金
- Cancer Research UK and European Research Council [281739]
Poly(ADP-ribosyl) ation is a post-translational protein modification involved in the regulation of important cellular functions including DNA repair, transcription, mitosis and apoptosis. The amount of poly(ADP-ribosyl) ation (PAR) in cells reflects the balance of synthesis, mediated by the PARP protein family, and degradation, which is catalyzed by a glycohydrolase, PARG. Many of the proteins mediating PAR metabolism possess specialised high affinity PAR-binding modules that allow the efficient sensing or processing of the PAR signal. The identification of four such PAR-binding modules and the characterization of a number of proteins utilising these elements during the last decade has provided important insights into how PAR regulates different cellular activities. The macrodomain represents a unique PAR-binding module which is, in some instances, known to possess enzymatic activity on ADP-ribose derivatives (in addition to PAR-binding). The most recently discovered example for this is the PARG protein, and several available PARG structures have provided an understanding into how the PARG macrodomain evolved into a major enzyme that maintains PAR homeostasis in living cells.
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