A systematic analysis of the PARP protein family identifies new functions critical for cell physiology

The poly(ADP-ribose) polymerase (PARP) family of proteins use NAD + as their substrate to modify acceptor proteins with ADP-ribose modifications. The function of most PARPs under physiological conditions is unknown. Here, to better understand this protein family, we systematically analyse the cell c...

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Bibliographic Details
Published in:Nature communications 2013, Vol.4 (1), p.2240-2240, Article 2240
Main Authors: Vyas, Sejal, Chesarone-Cataldo, Melissa, Todorova, Tanya, Huang, Yun-Han, Chang, Paul
Format: Article
Language:English
Subjects:
631/80/458/2389
Cell Adhesion
Cell Cycle
Cell Movement
Cell Nucleus - enzymology
Cell Physiological Phenomena
Cell Shape
Focal Adhesions - metabolism
Gene Expression Regulation, Enzymologic
Gene Knockdown Techniques
HeLa Cells
Humanities and Social Sciences
Humans
multidisciplinary
Phenotype
Poly Adenosine Diphosphate Ribose - metabolism
Poly(ADP-ribose) Polymerases - genetics
Poly(ADP-ribose) Polymerases - metabolism
Protein Transport
RNA, Messenger - genetics
RNA, Messenger - metabolism
Science
Science (multidisciplinary)
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Summary:The poly(ADP-ribose) polymerase (PARP) family of proteins use NAD + as their substrate to modify acceptor proteins with ADP-ribose modifications. The function of most PARPs under physiological conditions is unknown. Here, to better understand this protein family, we systematically analyse the cell cycle localization of each PARP and of poly(ADP-ribose), a product of PARP activity, then identify the knockdown phenotype of each protein and perform secondary assays to elucidate function. We show that most PARPs are cytoplasmic, identify cell cycle differences in the ratio of nuclear to cytoplasmic poly(ADP-ribose) and identify four phenotypic classes of PARP function. These include the regulation of membrane structures, cell viability, cell division and the actin cytoskeleton. Further analysis of PARP14 shows that it is a component of focal adhesion complexes required for proper cell motility and focal adhesion function. In total, we show that PARP proteins are critical regulators of eukaryotic physiology. The poly(ADP-ribose) polymerase (PARP) family includes 17 proteins in humans, many of which have no known function. Vyas et al. systematically characterize the localization and function of each human PARP and identify PARP14 as a regulator of focal adhesions.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms3240