A Phospho-SIM in the Antiviral Protein PML is Required for Its Recruitment to HSV-1 Genomes
AbstractHerpes simplex virus type 1 (HSV-1) is a significant human pathogen that infects a large portion of the human population. Cells deploy a variety of defenses to limit the extent to which the virus can replicate. One such factor is the promyelocytic leukemia (PML) protein, the nucleating and organizing factor of nuclear domain 10 (ND10). PML responds to a number of stimuli and is implicated in intrinsic and innate cellular antiviral defenses against HSV-1. While the role of PML in a number of cellular pathways is controlled by post-translational modifications, the effects of phosphorylation on its antiviral activity toward HSV-1 have been largely unexplored. Consequently, we mapped phosphorylation sites on PML, mutated these and other known phosphorylation sites on PML isoform I (PML-I), and examined their effects on a number of PML’s activities. Our results show that phosphorylation at most sites on PML-I is dispensable for the formation of ND10s and colocalization between PML-I and the HSV-1 regulatory protein, ICP0, which antagonizes PML-I function. However, inhibiting phosphorylation at sites near the SUMO-interaction motif (SIM) of PML-I impairs its ability to respond to HSV-1 infection. Overall, our data suggest that PML phosphorylation regulates its antiviral activity against HSV-1. View Full-Text
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Smith, M.C.; Box, A.C.; Haug, J.S.; Lane, W.S.; Davido, D.J. A Phospho-SIM in the Antiviral Protein PML is Required for Its Recruitment to HSV-1 Genomes. Cells 2014, 3, 1131-1158.
Smith MC, Box AC, Haug JS, Lane WS, Davido DJ. A Phospho-SIM in the Antiviral Protein PML is Required for Its Recruitment to HSV-1 Genomes. Cells. 2014; 3(4):1131-1158.Chicago/Turabian Style
Smith, Miles C.; Box, Andrew C.; Haug, Jeffrey S.; Lane, William S.; Davido, David J. 2014. "A Phospho-SIM in the Antiviral Protein PML is Required for Its Recruitment to HSV-1 Genomes." Cells 3, no. 4: 1131-1158.