A deneddylase encoded by Epstein-Barr virus promotes viral DNA replication by regulating the activity of cullin-RING ligases
Autor: | Mia Palmkvist, Maria G. Masucci, Sebastian Hildebrand, Omid R. Faridani, Stefano Gastaldello, Claudia Di Guglielmo, Simone Callegari |
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Rok vydání: | 2009 |
Předmět: |
DNA Replication
Herpesvirus 4 Human Time Factors viruses Recombinant Fusion Proteins Cell Cycle Proteins Transfection Virus Replication NEDD8 Virus S Phase DNA replication factor CDT1 Genes Reporter Humans Viral Regulatory and Accessory Proteins Ubiquitins biology DNA synthesis Protein Stability Hydrolysis DNA replication Cell Biology Cullin Proteins Molecular biology Cell biology Protein Structure Tertiary Licensing factor Viral replication DNA Viral biology.protein Cullin HeLa Cells |
Zdroj: | Nature cell biology. 12(4) |
ISSN: | 1476-4679 |
Popis: | The large tegument proteins of herpesviruses encode conserved cysteine proteases of unknown function. Here we show that BPLF1, the Epstein-Barr-virus-encoded member of this protease family, is a deneddylase that regulates virus production by modulating the activity of cullin-RING ligases (CRLs). BPLF1 hydrolyses NEDD8 conjugates in vitro, acts as a deneddylase in vivo, binds to cullins and stabilizes CRL substrates. Expression of BPLF1 alone or in the context of the productive virus cycle induces accumulation of the licensing factor CDT1 and deregulates S-phase DNA synthesis. Inhibition of BPLF1 during the productive virus cycle prevents cellular DNA re-replication and inhibits virus replication. Viral DNA synthesis is restored by overexpression of CDT1. Homologues encoded by other herpesviruses share the deneddylase activity. Thus, these enzymes are likely to have a key function in the virus life cycle by inducing a replication-permissive S-phase-like cellular environment. |
Databáze: | OpenAIRE |
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