The impact of PARPs and ADP-ribosylation on inflammation and host–pathogen interactions
- Anthony R. Fehr1,
- Sasha A. Singh2,
- Catherine M. Kerr1,
- Shin Mukai2,
- Hideyuki Higashi2 and
- Masanori Aikawa2,3,4
- 1Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045, USA;
- 2Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA;
- 3Center for Excellence in Vascular Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA;
- 4Department of Human Pathology, I.M. Sechenov First Moscow State Medical University of the Ministry of Health, Moscow 119146, Russian Federation
- Corresponding authors: maikawa{at}bwh.harvard.edu, arfehr{at}ku.edu
Abstract
Poly-adenosine diphosphate-ribose polymerases (PARPs) promote ADP-ribosylation, a highly conserved, fundamental posttranslational modification (PTM). PARP catalytic domains transfer the ADP-ribose moiety from NAD+ to amino acid residues of target proteins, leading to mono- or poly-ADP-ribosylation (MARylation or PARylation). This PTM regulates various key biological and pathological processes. In this review, we focus on the roles of the PARP family members in inflammation and host–pathogen interactions. Here we give an overview the current understanding of the mechanisms by which PARPs promote or suppress proinflammatory activation of macrophages, and various roles PARPs play in virus infections. We also demonstrate how innovative technologies, such as proteomics and systems biology, help to advance this research field and describe unanswered questions.
Keywords
- ADP-ribosylation
- PARP
- atherosclerosis
- host–pathogen interactions
- immunity
- inflammation
- macrophage
- vascular disease
Footnotes
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.334425.119.
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Freely available online through the Genes & Development Open Access option.
This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
