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  • Original Paper
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Herpes virus induced proteasome-dependent degradation of the nuclear bodies-associated PML and Sp100 proteins

Oncogene volume 18, pages 935–941 (1999)Cite this article

Abstract

The PML protein is associated to nuclear bodies (NBs) whose functions are as yet unknown. PML and two other NBs-associated proteins, Sp100 And ISG20 are directly induced by interferons (IFN). PML and Sp100 proteins are covalently linked to SUMO-1, and ubiquitin-like peptide. PML NBs are disorganized in acute promyelocytic leukemia and during several DNA virus infections. In particular, the HSV-1 ICP0 protein is known to delocalize PML from NBs. Thus, NBs could play an important role in oncogenesis, IFN response and viral infections. Here, we show that HSV-1 induced PML protein degradation without altering its mRNA level. This degradation was time- and multiplicity of infection-dependent. Sp100 protein was also degraded, while another SUMO-1 conjugated protein, RanGAP1 and the IFN-induced protein kinase PKR were not. The proteasome inhibitor MG132 abrogated the HSV-1-induced PML and Sp100 degradation and partially restored their NB-localization. HSV-1 induced PML and Sp100 degradation constitutes a new example of viral inactivation of IFN target gene products.

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Abbreviations

NBs:

nuclear bodies

IFN:

interferon

HSV-1:

herpes simplex virus type 1

PML:

ProMyelocytic Leukaemia

PIC-1:

PML interacting clone 1

SUMO:

small ubiquitin related modifier

HAUSP:

herpes virus-associated ubiquitin-specific protease

APL:

acute promyelocytic leukaemia

ISG-20:

interferon stimulated gene 20

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Acknowledgements

We thank C Chopin for technical assistance. We also thank F Melchoir for rabbit antiRanGAP1 antibodies and S Rees for the pCIN vector. The help of B Boursin for the artwork, and M Schmid for the confocal microscopy were highly appreciated. The work was supported by grants from ARC, Ligue contre le Cancer (Nationale, Comité del Paris et Hauts de Seine).

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  1. Centre National de la Recherche Scientifique Unité Propre de Recherche 9051, Laboratoire associé au Comité de Paris de la Ligue Contre le Cancer, Institut Universitaire d'Hématologie de l'université de Paris VII, France

    Mounira K Chelbi-Alix & Hugues de Thé

  2. Service de Biochimie B, Hôpital St Louis, Paris, France

    Hugues de Thé

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  1. Mounira K Chelbi-Alix
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  2. Hugues de Thé
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Chelbi-Alix, M., de Thé, H. Herpes virus induced proteasome-dependent degradation of the nuclear bodies-associated PML and Sp100 proteins. Oncogene 18, 935–941 (1999). https://doi.org/10.1038/sj.onc.1202366

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