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PMID:15247261

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Citation

Canning, M, Boutell, C, Parkinson, J and Everett, RD (2004) A RING finger ubiquitin ligase is protected from autocatalyzed ubiquitination and degradation by binding to ubiquitin-specific protease USP7. J. Biol. Chem. 279:38160-8

Abstract

Herpes simplex virus type 1 immediate-early regulatory protein ICP0 stimulates lytic infection and reactivation from latency, processes that require the ubiquitin E3 ligase activity mediated by the RING finger domain in the N-terminal portion of the protein. ICP0 stimulates the production of polyubiquitin chains by the ubiquitin-conjugating enzymes UbcH5a and UbcH6 in vitro, and in infected and transfected cells it induces the proteasome-dependent degradation of a number of cellular proteins including PML, the major constituent protein of PML nuclear bodies. However, ICP0 binds strongly to the cellular ubiquitin-specific protease USP7, a member of a family of proteins that cleave polyubiquitin chains and/or ubiquitin precursors. The region of ICP0 that is required for its interaction with USP7 has been mapped, and mutations in this domain reduce the functionality of ICP0. These findings pose the question: why does ICP0 include domains that are associated with the potentially antagonistic functions of ubiquitin conjugation and deconjugation? Here we report that although neither protein affected the intrinsic activities of the other in vitro, USP7 protected ICP0 from autoubiquitination in vitro, and their interaction can greatly increase the stability of ICP0 in vivo. These results demonstrate that RING finger-mediated autoubiquitination of ICP0 is biologically relevant and can be regulated by interaction with USP7. This principle may extend to a number of cellular RING finger E3 ubiquitin ligase proteins that have analogous interactions with ubiquitin-specific cleavage enzymes.

Links

PubMed Online version:10.1074/jbc.M402885200

Keywords

Animals; Baculoviridae/genetics; Baculoviridae/metabolism; Binding Sites; Blotting, Western; Catalysis; Cell Line; Cell Line, Tumor; Cell Separation; Endopeptidases/metabolism; Flow Cytometry; Glutathione Transferase/metabolism; Herpesvirus 1, Human/metabolism; Humans; Immediate-Early Proteins/metabolism; Insects; Iron-Binding Proteins/metabolism; Mutation; Plasmids/metabolism; Precipitin Tests; Protein Binding; Protein Structure, Tertiary; RNA, Small Interfering/metabolism; Transfection; Ubiquitin/chemistry; Ubiquitin/metabolism; Ubiquitin Thiolesterase; Ubiquitin-Conjugating Enzymes/metabolism; Ubiquitin-Protein Ligase Complexes/metabolism; Ubiquitin-Protein Ligases/chemistry; Ubiquitin-Protein Ligases/metabolism; Ubiquitin-Protein Ligases/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HHV11:ICP0

enables

GO:0005515: protein binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HHV11:ICP0

located_in

GO:0042025: host cell nucleus

ECO:0000303: author statement without traceable support used in manual assertion

C

Seeded From UniProt

complete

HHV11:ICP0

enables

GO:0004842: ubiquitin-protein transferase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HHV11:ICP0

involved_in

GO:0000209: protein polyubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HHV11:ICP0

part_of

GO:0042025: host cell nucleus

ECO:0000303: author statement without traceable support used in manual assertion

C

Seeded From UniProt

complete

HHV11:ICP0

involved_in

GO:0045732: positive regulation of protein catabolic process

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HHV11:ICP0

involved_in

GO:0019046: release from viral latency

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete


See also

References

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