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Mol Aspects Med. 2013 Dec;34(6):1066-87. doi: 10.1016/j.mam.2012.12.005. Epub 2012 Dec 23.

Reprogramming cellular events by poly(ADP-ribose)-binding proteins.

Author information

1
Centre de recherche du CHUQ - Pavillon CHUL - Cancer Axis, Laval University, Québec, QC, Canada G1V 4G2.
2
Genome Stability Laboratory, Laval University Cancer Research Center, Hôtel-Dieu de Québec, Québec, QC, Canada G1R 2J6.
3
Department of Molecular Biology, Cellular Biochemistry and Pathology, Faculty of Medicine, Laval University, Québec, QC, Canada G1V 0A6.
4
Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
5
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
6
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
7
Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
#
Contributed equally

Abstract

Poly(ADP-ribosyl)ation is a posttranslational modification catalyzed by the poly(ADP-ribose) polymerases (PARPs). These enzymes covalently modify glutamic, aspartic and lysine amino acid side chains of acceptor proteins by the sequential addition of ADP-ribose (ADPr) units. The poly(ADP-ribose) (pADPr) polymers formed alter the physico-chemical characteristics of the substrate with functional consequences on its biological activities. Recently, non-covalent binding to pADPr has emerged as a key mechanism to modulate and coordinate several intracellular pathways including the DNA damage response, protein stability and cell death. In this review, we describe the basis of non-covalent binding to pADPr that has led to the emerging concept of pADPr-responsive signaling pathways. This review emphasizes the structural elements and the modular strategies developed by pADPr-binding proteins to exert a fine-tuned control of a variety of pathways. Poly(ADP-ribosyl)ation reactions are highly regulated processes, both spatially and temporally, for which at least four specialized pADPr-binding modules accommodate different pADPr structures and reprogram protein functions. In this review, we highlight the role of well-characterized and newly discovered pADPr-binding modules in a diverse set of physiological functions.

KEYWORDS:

Macro domain; PARG; PARP; PBZ; Poly(ADP-ribose); WWE

PMID:
23268355
PMCID:
PMC3812366
DOI:
10.1016/j.mam.2012.12.005
[Indexed for MEDLINE]
Free PMC Article

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