Requirements for the Nuclear-Cytoplasmic Translocation of Infected-Cell Protein 0 of Herpes Simplex Virus 1

Lopez, Pascal; Sant, Charles Van; Roizman, Bernard

doi:10.1128/jvi.75.8.3832-3840.2001

Cited by 88 publications

(136 citation statements)

References 32 publications

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“…In these cells, ICP0 is translocated to the cytoplasm very early after infection and aggregates into dense bodies shown in Fig. 4 a H and I and b T and U as dense punctate structures (20). In cells infected with the ⌬ICP4 mutant, CoREST was localized to the nucleus, and its distribution was not different from that of mock-infected cells.…”

Section: Corest Is Posttranslationally Modified After Infection With mentioning

confidence: 83%

“…5. Earlier studies have shown that ICP0 is translocated from nucleus to cytoplasm between 5 and 9 h after infection (20). Because only a fraction of CoREST was translocated, we quantified the distributions of CoREST and ICP0 either in the nucleus only or in both nucleus and cytoplasm of cells infected with either wild-type or mutant virus.…”

Section: Corest Is Posttranslationally Modified After Infection With mentioning

confidence: 99%

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Components of the REST/CoREST/histone deacetylase repressor complex are disrupted, modified, and translocated in HSV-1-infected cells

Liang

Mandel

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Section: Corest Is Posttranslationally Modified After Infection With mentioning

confidence: 83%

Section: Corest Is Posttranslationally Modified After Infection With mentioning

confidence: 99%

Components of the REST/CoREST/histone deacetylase repressor complex are disrupted, modified, and translocated in HSV-1-infected cells

Liang

Mandel

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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236

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“…In addition to the interaction of USP7 with the carboxy terminus, ICP0 dynamically associates with the 26S proteasome in untreated cells but remains bound to proteasomes in cells treated with the proteasome inhibitor MG132 (17,18). ICP0 similarly promotes the dynamic association of the E2 enzyme cdc34 with the proteasome in a manner dependent on aspartate 199 (17).…”

mentioning

confidence: 98%

Herpes simplex virus 1-infected cell protein 0 contains two E3 ubiquitin ligase sites specific for different E2 ubiquitin-conjugating enzymes

Hagglund

Sant

Lopez

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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Infected cell protein 0 (ICP0) of herpes simplex virus 1, a multifunctional ring finger protein, enhances the expression of genes introduced into cells by infection or transfection, interacts with numerous cellular and viral proteins, and is associated with the degradation of several cellular proteins. Sequences encoded by exon 2 of ICP0 (residues 20 -241) bind the UbcH3 (cdc34) ubiquitinconjugating enzyme, and its carboxy terminus expresses a ubiquitin ligase activity demonstrable by polyubiquitylation of cdc34 in vitro. We report that: (i) The physical interaction of cdc34 and ICP0 leads to its degradation. Thus, substitution of ICP0 aspartate 199 with alanine attenuates the degradation of cdc34 and its binding to the ICP0 ring finger domain. (ii) Substitution of residue 620 reported to abolish the interaction with a ubiquitin-specific protease has no effect on the function of ubiquitin ligase. (iii) ICP0 contains an additional distinct E3 ligase activity specific for the UbcH5a-and UbcH6 E2-conjugating enzymes mapping to the ring finger domain. This is, to our knowledge, the first identification of a viral protein with at least two physically separated E3 ligase activities with different E2 specificities. The results suggest that each activity may target different proteins.I nfected cell protein 0 (ICP0) of herpes simplex virus 1 (HSV-1) is essential for viral replication in cells infected at low multiplicity but is not essential in cells infected at high multiplicity (1-3). The 775-amino acid protein is translated from a spliced mRNA containing three exons encoding 19, 222, and 534 codons, respectively. The interaction of ICP0 with several diverse cellular proteins including the BMAL1 transactivator (4), the translation elongation factor 1␦ (5), cyclin D3 (6), and the ubiquitin (Ub)-specific protease USP7 (7-9), suggests that its phenotype as a promiscuous transactivator reflects the sum of its multiple and diverse functions. Early in infection, ICP0 localizes with the promyelocytic leukemia protein and causes the disruption of ND10 structures (10-13). A zinc-binding RING finger (amino acids 106-149) characteristic of E3 Ub ligase enzymes has been identified in the domain encoded by exon 2 (14).Analyses of ICP0 in the yeast two-hybrid system led to the discovery that ICP0 binds and stabilizes cyclin D3 (6). Mapping studies led to the identification of aspartate 199 as pivotal for both stabilization and binding of cyclin D3. Replacement of aspartate 199 with alanine (D199A) abolishes both binding and stabilization of cyclin D3 mediated by ICP0 and results in attenuated viral growth in quiescent human embryonic lung fibroblasts and reduced neuroinvasiveness (15,16). These studies also revealed that ICP0 stabilizes cyclin D1 in a manner dependent on aspartate 199, even though it does not interact with it in vitro or in the yeast two-hybrid system (15, 16). Because HSV-1 replicates well in both dividing and stationary cells, these observations were pursued at several levels. The transcription of cyclin D3 or D1 ...

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“…Translocation of ICP0 also requires a late (␥ 1 ) gene expression inasmuch as inhibitors of viral DNA synthesis delay the translocation of ICP0. The ICP0 interacts dynamically with proteasomal components, inasmuch as exposure of infected cells to proteasomal inhibitor MG132 before 5 h of infection precludes the translocation to the cytoplasm, whereas exposure of infected cells to MG132 at 9 h after infection results in quantitative relocation of ICP0 from the cytoplasm to the nucleus (10). The second set of observations centers on complementation studies of HSV-1 mutants.…”

mentioning

confidence: 99%

“…Briefly, ICP0 is translocated to the cytoplasm between 5 and 9 h after infection (10). The translocation of ICP0 to the cytoplasm involves three distinct events.…”

mentioning

confidence: 99%

Nuclear retention of ICP0 in cells exposed to HDAC inhibitor or transfected with DNA before infection with herpes simplex virus 1

Kalamvoki¹,

Roizman²

2008

Proc. Natl. Acad. Sci. U.S.A.

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The ␣ (immediate early) protein ICP0 of herpes simplex virus 1 enhances the expression of genes introduced by infection or transfection. Early in infection it performs two key functions: It blocks the silencing of the viral DNA by cellular proteins and it blocks the IFN stimulated host response to infection. Between 5 and 9 h after infection, ICP0 is translocated to the cytoplasm but remains dynamically associated with proteasomes. In this report we show that in permissive cells that are poor expressors of transfected genes (HEp-2, U2OS, etc.), ICP0 is retained in the nucleus if the cells had been transfected with DNA and then infected. The retention is DNA dose-and size-dependent but not DNA type-dependent. Retention of ICP0 is also a consequence of infection with wild-type virus concomitant with exposure of cells to sodium butyrate. ICP0 is not retained in transfected/infected cells that efficiently express transfected genes (HEK293, rabbit skin cells). The retention of ICP0 in the nucleus is concordant with failure to degrade PML and disperse ND10 structures, and delays in the transition to post ␣ genes expression, translocation of components of the CoREST/REST/HDAC1 complex and histone relocation in the infected cell. The data suggest that (i) retention of ICP0 is linked to its function to remodel acetylated DNA but not DNA in heterochromatin. This function is independent of response elements embedded in the DNA and (ii) transfection-resistant cells do take up DNA but process it differently than cells that readily express transfected genes.DNA transfection ͉ ND10 bodies ͉ silencing T his report centers on ICP0, an ␣ (immediate early) protein specified by herpes simplex virus 1 (HSV-1). ICP0 interacts with many diverse cellular and viral proteins and acts as a promiscuous transactivator of genes introduced into cells by transfection or infection (1-3). Its two most prominent functions are to render the infected cells resistant to antiviral activity of interferons and to block the silencing of viral DNA (4-7). At the molecular level, it acts as an E3 ubiquitin ligase to degrade PML and SP100. In consequence the components of ND10 nuclear bodies are dispersed (8, 9). In addition ICP0 blocks the silencing of viral DNA through dissociation of the HDAC1 or 2 from the CoREST/REST/LSD1 complex. The components of the complex are then translocated to the cytoplasm (5).The genesis of current studies stemmed from two sets of observations. Briefly, ICP0 is translocated to the cytoplasm between 5 and 9 h after infection (10). The translocation of ICP0 to the cytoplasm involves three distinct events. Thus, ICP0 interacts with cyclin D3. Overexpression of cyclin D3 accelerates the translocation whereas substitution of D199 with alanine abolishes the interaction with cyclin D3 and results in the retention of ICP0 in the nucleus (11). The mutant carrying the D199A substitution replicates efficiently. Translocation of ICP0 also requires a late (␥ 1 ) gene expression inasmuch as inhibitors of viral DNA synthesis delay the trans...

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Requirements for the Nuclear-Cytoplasmic Translocation of Infected-Cell Protein 0 of Herpes Simplex Virus 1

Cited by 88 publications

References 32 publications

Components of the REST/CoREST/histone deacetylase repressor complex are disrupted, modified, and translocated in HSV-1-infected cells

Components of the REST/CoREST/histone deacetylase repressor complex are disrupted, modified, and translocated in HSV-1-infected cells

Herpes simplex virus 1-infected cell protein 0 contains two E3 ubiquitin ligase sites specific for different E2 ubiquitin-conjugating enzymes

Nuclear retention of ICP0 in cells exposed to HDAC inhibitor or transfected with DNA before infection with herpes simplex virus 1

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