Functional interactions between the Epstein-Barr virus BZLF1 protein and the promyelocytic leukemia protein

Virus Res. 2006 May;117(2):244-53. doi: 10.1016/j.virusres.2005.10.018. Epub 2005 Nov 22.

Abstract

The Epstein-Barr virus immediate-early protein BZLF1 (Z) has been shown to alter the cellular localization of the promyelocytic leukemia (PML) protein. PML has important implications for growth control, apoptosis, anti-viral effects and many more processes. Here we further examined the relationship between PML and the Epstein-Barr virus Z protein. We examined the effect of Z expression on PML protein levels, and the effect of increased PML protein levels on Z-mediated dispersion of PML bodies. We found that increased levels of PML protein, such as through interferon treatment, were able to suppress Z-mediated PML body dispersion. We also studied the consequences of PML dispersion by Z, by examining p21 transactivation, A20 transactivation, and MHC Class I presentation levels in Z-expressing cells. We found that, while Z-mediated dispersion of PML did not affect MHC Class I presentation, it did alter p21 and A20 expression. In addition, we found that increased levels of PML were able to prevent Z protein binding to mitotic chromosomes. Our work implies that the balance of PML and Z levels in cells may affect how each protein functions.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Artificial Gene Fusion
  • Blotting, Western
  • Chromosomes / chemistry
  • DNA-Binding Proteins / metabolism*
  • Gene Expression
  • Genes, Reporter
  • HeLa Cells
  • Histocompatibility Antigens Class I / physiology
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Luciferases / analysis
  • Luciferases / genetics
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Neoplasm Proteins / metabolism*
  • Nuclear Proteins / metabolism*
  • Promyelocytic Leukemia Protein
  • Protein Binding
  • Proteins / analysis
  • Trans-Activators / metabolism*
  • Transcription Factors / metabolism*
  • Transcriptional Activation
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • Tumor Suppressor Proteins / analysis
  • Tumor Suppressor Proteins / metabolism*
  • Viral Proteins / metabolism*

Substances

  • BZLF1 protein, Herpesvirus 4, Human
  • DNA-Binding Proteins
  • Histocompatibility Antigens Class I
  • Intracellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • Nuclear Proteins
  • Promyelocytic Leukemia Protein
  • Proteins
  • Trans-Activators
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Viral Proteins
  • PML protein, human
  • Luciferases
  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3