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Virus-Cell Interactions

Herpes Simplex Virus Type 1 Immediate-Early Protein ICP0 and Its Isolated RING Finger Domain Act as Ubiquitin E3 Ligases In Vitro

Chris Boutell, Seth Sadis, Roger D. Everett
Chris Boutell
1Medical Research Council Virology Unit, Glasgow G11 5JR, Scotland, United Kingdom
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Seth Sadis
2Millenium Pharmaceuticals Inc., Cambridge, Massachusetts
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Roger D. Everett
1Medical Research Council Virology Unit, Glasgow G11 5JR, Scotland, United Kingdom
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  • For correspondence: r.everett@vir.gla.ac.uk
DOI: 10.1128/JVI.76.2.841-850.2002
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ABSTRACT

Proteasome-dependent degradation of ubiquitinated proteins plays a key role in many important cellular processes. Ubiquitination requires the E1 ubiquitin activating enzyme, an E2 ubiquitin conjugating enzyme, and frequently a substrate-specific ubiquitin protein ligase (E3). One class of E3 ubiquitin ligases has been shown to contain a common zinc-binding RING finger motif. We have previously shown that herpes simplex virus type 1 ICP0, itself a RING finger protein, induces the proteasome-dependent degradation of several cellular proteins and induces the accumulation of colocalizing conjugated ubiquitin in vivo. We now report that both full-length ICP0 and its isolated RING finger domain induce the accumulation of polyubiquitin chains in vitro in the presence of E1 and the E2 enzymes UbcH5a and UbcH6. Mutations within the RING finger region that abolish the in vitro ubiquitination activity also cause severe reductions in ICP0 activity in other assays. We conclude that ICP0 has the potential to act as an E3 ubiquitin ligase during viral infection and to target specific cellular proteins for destruction by the 26S proteasome.

  • Copyright © 2002 American Society for Microbiology
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Herpes Simplex Virus Type 1 Immediate-Early Protein ICP0 and Its Isolated RING Finger Domain Act as Ubiquitin E3 Ligases In Vitro
Chris Boutell, Seth Sadis, Roger D. Everett
Journal of Virology Jan 2002, 76 (2) 841-850; DOI: 10.1128/JVI.76.2.841-850.2002

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Herpes Simplex Virus Type 1 Immediate-Early Protein ICP0 and Its Isolated RING Finger Domain Act as Ubiquitin E3 Ligases In Vitro
Chris Boutell, Seth Sadis, Roger D. Everett
Journal of Virology Jan 2002, 76 (2) 841-850; DOI: 10.1128/JVI.76.2.841-850.2002
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KEYWORDS

Herpesvirus 1, Human
Immediate-Early Proteins
Iron-Binding Proteins
Ligases
Proteasome Endopeptidase Complex
Ubiquitin-Conjugating Enzymes

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