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

Oncogene. 1999 Jan 28;18(4):935-41. doi: 10.1038/sj.onc.1202366.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Nuclear*
  • Autoantigens / chemistry
  • Autoantigens / metabolism*
  • Carrier Proteins / metabolism
  • Cysteine Proteinase Inhibitors / pharmacology
  • GTPase-Activating Proteins*
  • Herpes Simplex / metabolism*
  • Herpesvirus 1, Human*
  • Humans
  • Interferons / pharmacology
  • Leupeptins / pharmacology
  • Molecular Weight
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / metabolism*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Promyelocytic Leukemia Protein
  • Protein Kinases / metabolism
  • RNA, Messenger / metabolism
  • SUMO-1 Protein
  • Time Factors
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins
  • Ubiquitins / metabolism

Substances

  • Antigens, Nuclear
  • Autoantigens
  • Carrier Proteins
  • Cysteine Proteinase Inhibitors
  • GTPase-Activating Proteins
  • Leupeptins
  • Neoplasm Proteins
  • Nuclear Proteins
  • Promyelocytic Leukemia Protein
  • RANGAP1 protein, human
  • RNA, Messenger
  • SUMO-1 Protein
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Ubiquitins
  • Sp100 protein, human
  • PML protein, human
  • Interferons
  • Protein Kinases
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde