SUMOylation Promotes PML Degradation during Encephalomyocarditis Virus Infection
Autor: | Manuel S. Rodriguez, Mounira K. Chelbi-Alix, Mohamed-Ali Maroui, Nicolas Escriou, Laurent Dianoux, Tarik Regad, Sylvie Gerbaud, A. G. Aminev, Bouchra El Mchichi |
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Rok vydání: | 2010 |
Předmět: |
viruses
Intranuclear Inclusion Bodies Immunology SUMO protein Cellular Response to Infection CHO Cells Promyelocytic Leukemia Protein Biology environment and public health Microbiology Cell Line Mice Promyelocytic leukemia protein Cricetulus Cricetinae Virology Cardiovirus Infections medicine Animals Humans Encephalomyocarditis virus Nuclear protein Cell Nucleus Mice Knockout Nucleoplasm Tumor Suppressor Proteins Nuclear Proteins virus diseases Nuclear matrix Protein Transport Cell nucleus medicine.anatomical_structure Proteasome Cytoplasm Insect Science embryonic structures Small Ubiquitin-Related Modifier Proteins biology.protein Protein Processing Post-Translational Transcription Factors |
Zdroj: | Journal of Virology. 84:11634-11645 |
ISSN: | 1098-5514 0022-538X |
DOI: | 10.1128/jvi.01321-10 |
Popis: | The promyelocytic leukemia (PML) protein is expressed in the diffuse nuclear fraction of the nucleoplasm and in matrix-associated structures, known as nuclear bodies (NBs). PML NB formation requires the covalent modification of PML to SUMO. The noncovalent interactions of SUMO with PML based on the identification of a SUMO-interacting motif within PML seem to be required for further recruitment within PML NBs of SUMOylated proteins. RNA viruses whose replication takes place in the cytoplasm and is inhibited by PML have developed various strategies to counteract the antiviral defense mediated by PML NBs. We show here that primary fibroblasts derived from PML knockout mice are more sensitive to infection with encephalomyocarditis virus (EMCV), suggesting that the absence of PML results in an increase in EMCV replication. Also, we found that EMCV induces a decrease in PML protein levels both in interferon-treated cells and in PMLIII-expressing cells. Reduction of PML was carried out by the EMCV 3C protease. Indeed, at early times postinfection, EMCV induced PML transfer from the nucleoplasm to the nuclear matrix and PML conjugation to SUMO-1, SUMO-2, and SUMO-3, leading to an increase in PML body size where the viral protease 3C and the proteasome component were found colocalizing with PML within the NBs. This process was followed by PML degradation occurring in a proteasome- and SUMO-dependent manner and did not involve the SUMO-interacting motif of PML. Together, these findings reveal a new mechanism evolved by EMCV to antagonize the PML pathway in the interferon-induced antiviral defense. |
Databáze: | OpenAIRE |
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