Murine gammaherpesvirus 68 ORF75c contains ubiquitin E3 ligase activity and requires PML SUMOylation but not other known cellular PML regulators, CK2 and E6AP, to mediate PML degradation
| Autor: | Jaturong Sewatanon, Paul D. Ling |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Rhadinovirus
viruses Ubiquitin-Protein Ligases SUMO protein Promyelocytic Leukemia Protein Article Cell Line 03 medical and health sciences Promyelocytic leukemia protein Mice Ubiquitin Virology Protein Interaction Mapping Animals Humans Viral ubiquitin E3 ligase Gene 030304 developmental biology 0303 health sciences ORF75c biology Tumor Suppressor Proteins 030302 biochemistry & molecular biology virus diseases Nuclear Proteins Sumoylation Transfection Molecular biology Ubiquitin ligase Proteasome Formylglycinamide ribonucleotide amidotransferase (FGARAT) SUMO Murine gammaherpesvirus 68 Host-Pathogen Interactions Proteolysis biology.protein Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor Casein kinase 2 Protein Processing Post-Translational Transcription Factors |
| Zdroj: | Virology. 440(2):140-149 |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/j.virol.2013.02.014 |
| Popis: | All gammaherpsviruses encode at least one gene related to the cellular formylglycinamide ribonucleotide amidotransferase (FGARAT) enzyme but their biological roles are relatively unknown. The murine gammaherpesvirus 68 (MHV68) vFGARAT, ORF75c, mediates a proteasome-dependent degradation of the antiviral promyelocytic leukemia (PML) protein by an unknown mechanism, which is addressed in this study. We found that ORF75c interacts weakly with PML and SUMO-modified forms of PML are important for its degradation by ORF75c. ORF75c-mediated PML degradation was not dependent on two known cellular regulators of PML stability, Casein kinase II (CK2) and human papilloma virus E6-associated protein (E6AP). Finally, ORF75c had self-ubiquitination activity in vitro and its expression increased levels of ubiquitinated PML in transfected cells. Taken together, the evidence accumulated in this study provides new insights into the function of a vFGARAT and is consistent with a model in which ORF75c could mediate direct ubiquitination of PML resulting in its degradation by the proteasome. |
| Databáze: | OpenAIRE |
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