The p127 Subunit (DDB1) of the UV-DNA Damage Repair Binding Protein Is Essential for the Targeted Degradation of STAT1 by the V Protein of the Paramyxovirus Simian Virus 5
- 15 November 2002
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 76 (22), 11379-86
- https://doi.org/10.1128/jvi.76.22.11379-11386.2002
Abstract
The V protein of simian virus 5 (SV5) blocks interferon signaling by targeting STAT1 for proteasome-mediated degradation. Here we present three main pieces of evidence which demonstrate that the p127 subunit (DDB1) of the UV damage-specific DNA binding protein (DDB) plays a central role in this degradation process. First, the V protein of an SV5 mutant which fails to target STAT1 for degradation does not bind DDB1. Second, mutations in the N and C termini of V which abolish the binding of V to DDB1 also prevent V from blocking interferon (IFN) signaling. Third, treatment of HeLa/SV5-V cells, which constitutively express the V protein of SV5 and thus lack STAT1, with short interfering RNAs specific for DDB1 resulted in a reduction in DDB1 levels with a concomitant increase in STAT1 levels and a restoration of IFN signaling. Furthermore, STAT1 is degraded in GM02415 (2RO) cells, which have a mutation in DDB2 (the p48 subunit of DDB) which abolishes its ability to interact with DDB1, thereby demonstrating that the role of DDB1 in STAT1 degradation is independent of its association with DDB2. Evidence is also presented which demonstrates that STAT2 is required for the degradation of STAT1 by SV5. These results suggest that DDB1, STAT1, STAT2, and V may form part of a large multiprotein complex which leads to the targeted degradation of STAT1 by the proteasome.Keywords
This publication has 61 references indexed in Scilit:
- High Resistance of Human Parainfluenza Type 2 Virus Protein-Expressing Cells to the Antiviral and Anti-Cell Proliferative Activities of Alpha/Beta Interferons: Cysteine-Rich V-Specific Domain Is Required for High Resistance to the InterferonsJournal of Virology, 2001
- The virus battles: IFN induction of the antiviral state and mechanisms of viral evasionCytokine & Growth Factor Reviews, 2001
- C Terminal CYS-RICH Region of Mumps Virus Structural V Protein Correlates with Block of Interferon α and γ Signal Transduction Pathway through Decrease of STAT 1-αBiochemical and Biophysical Research Communications, 2001
- Single Amino Acid Substitution in the V Protein of Simian Virus 5 Differentiates Its Ability To Block Interferon Signaling in Human and Murine CellsJournal of Virology, 2001
- Correct binding of viral X protein to UVDDB-p127 cellular protein is critical for efficient infection by hepatitis B virusesOncogene, 2000
- Reinvestigation of the Classification of Five Cell Strains of Xeroderma Pigmentosum Group E with Reclassification of Three of ThemJournal of Investigative Dermatology, 2000
- Knockout of the Sendai virus C gene eliminates the viral ability to prevent the interferon‐α/β‐mediated responsesFEBS Letters, 1999
- A 127‐kDa Protein (UV‐DDB) Binds to the Cytoplasmic Domain of the Alzheimer's Amyloid Precursor ProteinJournal of Neurochemistry, 1999
- Studies on the transformation of intact yeast cells by the LiAc/SS‐DNA/PEG procedureYeast, 1995
- Identification of an epitope on the P and V proteins of simian virus 5 that distinguishes between two isolates with different biological characteristicsJournal of General Virology, 1991