An epitope within the DNA-binding domain of the herpes simplex virus immediate early protein Vmw175 is conserved in the varicella-zoster virus gene 62 protein

Everett, Roger D.; Cross, A. M.; Tyler, Jess; Orr, Anne

doi:10.1099/0022-1317-74-9-1955

Cited by 14 publications

(8 citation statements)

References 7 publications

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“…E. coli for expression of a GST/ATF-2-(19 -96) fusion protein, purified GST/ATF-2 (19 -96), purified recombinant 6-his-JNK/SAPK, and antibodies for the immunoprecipitation of SKK 1 and SKK 4 (9) were obtained from Dr. S. Lawler, MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, Dundee, UK. Antibodies for the detection of Vmw110 and Vmw175 in Western blotting were obtained from Dr. R. Everett (37,38). Antibodies specific for R1 and Vmw63 proteins were as described (39,40).…”

Section: Methodsmentioning

confidence: 99%

Herpes Simplex Virus Type 1 Infection Stimulates p38/c-Jun N-terminal Mitogen-activated Protein Kinase Pathways and Activates Transcription Factor AP-1

Zachos

Clements

Conner

1999

Journal of Biological Chemistry

157

152

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Cells respond to environmental stress and proinflammatory cytokines by stimulating the Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) and the p38 mitogen-activated protein kinase cascades. Infection of eukaryotic cells with herpes simplex virus type 1 (HSV-1) resulted in stimulation of both JNK/SAPK and p38 mitogen-activated protein kinase after 3 h of infection, and activation reached a maximum of 4-fold by 9 h post-infection. By using a series of mutant viruses, we showed that the virion transactivator protein VP16 stimulates p38/JNK, whereas no immediate-early, early, or late viral expressed gene is involved. We identified the stress-activated protein kinase kinase 1 as an upstream activator of p38/JNK, and we demonstrated that activation of AP-1 binding proceeded p38/JNK stimulation. During infection, the activated AP-1 consisted mainly of JunB and JunD with a simultaneous decrease in the cellular levels of Jun protein. We suggest that activation of the stress pathways by HSV-1 infection either represents a cascade triggered by the virus to facilitate the lytic cycle or a defense mechanism of the host cell against virus invasion.

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Section: Methodsmentioning

confidence: 99%

Herpes Simplex Virus Type 1 Infection Stimulates p38/c-Jun N-terminal Mitogen-activated Protein Kinase Pathways and Activates Transcription Factor AP-1

Zachos

Clements

Conner

1999

Journal of Biological Chemistry

157

152

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“…After blocking overnight at 4°C in PBS containing 0.1% Tween 20 (PBST) and 5% dried milk, the membranes were incubated with primary antibody in PBST containing 5% dried milk for 2 h at room temperature. The antibodies used were: anti-ICP0 mAb 11060 (28), anti-ICP4 mAb 10176 (29), anti-USP7 rabbit serum r201 (30) or BL851 (Bethyl Laboratories), and anti-ubiquitin antibody P4D1 (Santa Cruz Biotechnology). The membranes were washed four times in PBST, incubated with secondary antibody in PBST and 2% dried milk for one h at room temperature, washed four times in PBST, and then incubated with PerkinElmer Life Sciences Enhanced ECL reagent and exposed to film.…”

Section: Aag Aat Cag Ggc Gcc Act Agt Tac Atg Aacmentioning

confidence: 99%

A RING Finger Ubiquitin Ligase Is Protected from Autocatalyzed Ubiquitination and Degradation by Binding to Ubiquitin-specific Protease USP7

Canning

Boutell

Parkinson

et al. 2004

Journal of Biological Chemistry

127

122

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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.Herpes simplex virus type 1 (HSV-1) 1 is a common human pathogen that can establish a lifelong quiescent infection in sensory neurons following primary infection of epithelial cells. Environmental stimuli such as stress and sunlight trigger periodic recurrences of lytic infection, causing cold sores and genital lesions. HSV-1 expresses three broad groups of temporally regulated genes during lytic infection, termed immediate-early (IE), early, and late (for reviews, see Refs. 1 and 2). The IE protein ICP0 has an important role in the mechanisms that govern the switch between lytic and latent infection (reviewed in Refs. 3-5). Although not essential for viral replication, ICP0 increases the probability of the virus entering lytic infection, particularly after low multiplicity infection of human fibroblasts, and in its absence, viral genomes are more likely to become repressed and establish a quiescent infection (5-7). ICP0 stimulates the expression of all three classes of viral genes by as yet uncertain mechanisms that correlate with its ability to induce the degradation of a number of cellular proteins (8 -12). ICP0 includes a zinc-binding RING finger domain in its N-terminal portion, and in its C-terminal third lie a nuclear localization signal and motifs required for self-multimerization and efficient localization at specific nuclear substructures known as ND10 or PML nuclear bodies. Consistent with its ability to induce the degradation of...

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“…Proteins in 30 l of cell extract (equivalent to 6 ϫ 10 4 cells) were resolved in SDS-7.5 and/or 10% PAGE or 4 to 12% Bis-Tris NuPAGE gels (Invitrogen) and then transferred to nitrocellulose membranes by Western blotting. The filters were probed with the following antibodies, as appropriate: anti-ICP0 monoclonal antibody (MAb) 11060 (26), anti-ICP4 MAb 11076 (16), and anti-ICP27 MAb H1113 (1), purchased from the Goodwin Institute for Cancer Research; and an anti-p53 MAb (oncogene Ab-6), anti-actin MAb AC-40 (Sigma-Aldrich), and phospho-specific (p-) anti-p53 rabbit antibodies p-p53(Ser15) (Oncogene) and p-p53(hser20) (Santa Cruz Biotechnology).…”

Section: Cells and Viruses U2os And Hfff-2 Cells (European Collectiomentioning

confidence: 99%

Herpes Simplex Virus Type 1 Infection Induces the Stabilization of p53 in a USP7- and ATM-Independent Manner

Boutell

Everett

2004

J Virol

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The major oncoprotein p53 regulates several cellular antiproliferation pathways that can be triggered in response to a variety of cellular stresses, including viral infection. The stabilization of p53 is a key factor in the ability of cells to initiate an efficient transcriptional response after cellular stress. Here we present data demonstrating that herpes simplex virus type 1 (HSV-1) infection of HFFF-2 cells, a low-passage-number nontransformed human primary cell line, results in the stabilization of p53. This process required viral immediate-early gene expression but occurred independently of the viral regulatory protein ICP0 and viral DNA replication. No specific viral protein could be identified as being solely responsible for the effect, which appears to be a cellular response to developing HSV-1 infections. HSV-1 infection also induced the phosphorylation of p53 at residues Ser15 and Ser20, which have previously been implicated in its stabilization in response to DNA damage. However, an HSV-1 infection of ATM ؊/؊ cells, which lack a kinase implicated in these phosphorylation events, did not lead to the phosphorylation of p53 at these residues, but nonetheless p53 was stabilized. We also show that the wild-type p53 expressed by osteosarcoma U2OS cells can be stabilized in response to DNA damage induced by UV irradiation, but not in response to HSV-1 infection. These data suggest that multiple cellular mechanisms are initiated to stabilize p53 during an HSV-1 infection. These mechanisms occur independently of ICP0 and its ability to sequester USP7 and may differ from those initiated in response to DNA damage.The major oncoprotein p53 is a key regulator of the ability of cells to respond to stress through its control of several important cellular pathways, including growth arrest, apoptosis, and cellular senescence. The activation of p53 is induced by a variety of stresses, including DNA damage, hypoxia, nucleotide deprivation, heat shock, oncogenic activation, and viral infection. The ability of p53 to induce the transcription of several cellular genes is regulated by three principal factors, namely p53's stability, activity, and subcellular localization (for recent reviews, see references 12, 75, 77, and 79). The expression of p53 is normally maintained at low levels through ubiquitination and proteasome-mediated degradation (51). Although it appears that several ubiquitin isopeptide ligases (E3 ubiquitin ligases) are involved in p53 regulation (8,45), the best characterized of these is mouse double minute 2 (Mdm2). Mdm2 binds to the N terminus of p53, and in conjunction with the E2 ubiquitin-conjugating enzyme UbcH5, mediates the ubiquitination of C-terminal lysine residues of p53 and subsequent p53 degradation by the 26S proteasome (31,32,37,63). Consequently, the stabilization of p53 is critical for its ability to activate transcription. Stabilization of p53 can occur through several mechanisms, including phosphorylation of p53 at Nterminal serine (Ser) and threonine (Thr) residues (6, 41, 68, 69); ac...

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An epitope within the DNA-binding domain of the herpes simplex virus immediate early protein Vmw175 is conserved in the varicella-zoster virus gene 62 protein

Cited by 14 publications

References 7 publications

Herpes Simplex Virus Type 1 Infection Stimulates p38/c-Jun N-terminal Mitogen-activated Protein Kinase Pathways and Activates Transcription Factor AP-1

Herpes Simplex Virus Type 1 Infection Stimulates p38/c-Jun N-terminal Mitogen-activated Protein Kinase Pathways and Activates Transcription Factor AP-1

A RING Finger Ubiquitin Ligase Is Protected from Autocatalyzed Ubiquitination and Degradation by Binding to Ubiquitin-specific Protease USP7

Herpes Simplex Virus Type 1 Infection Induces the Stabilization of p53 in a USP7- and ATM-Independent Manner

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