This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lees-Miller, S. P. Articles by Spencer, C. A. Search for Related Content PubMed PubMed Citation Articles by Lees-Miller, S. P. Articles by Spencer, C. A.

 Previous Article  |  Next Article 

J. Virol., Nov 1996, 7471-7477, Vol 70, No. 11
Copyright © 1996, American Society for Microbiology

Attenuation of DNA-dependent protein kinase activity and its catalytic subunit by the herpes simplex virus type 1 transactivator ICP0

SP Lees-Miller, MC Long, MA Kilvert, V Lam, SA Rice and CA Spencer
Department of Biological Sciences, University of Calgary, Alberta, Canada.

The DNA-dependent protein kinase (DNA-PK) is involved in several fundamental nuclear processes, including DNA double-strand break repair, V(D)J recombination, and transcription by RNA polymerases I and II. In this study, we show that infection of mammalian cells with herpes simplex virus type 1 attenuates DNA-PK activity by specifically depleting the p350/DNA-PKcs catalytic subunit. The half-life of the p350/DNA-PKcs protein decreases from greater than 24 h to less than 4 h following infection. The depletion of DNA-PK activity and p350/DNA-PKcs abundance is dependent on expression of the viral immediate-early protein ICP0. As ICP0 acts as a promoter-independent transactivator of gene expression, these data suggest that ICP0 may function by directly or indirectly targeting the p350/DNA-PKcs subunit of DNA-PK, thereby altering the inhibitory effects of DNA-PK on RNA polymerase II transcription.

This article has been cited by other articles:

• Iwahori, S., Shirata, N., Kawaguchi, Y., Weller, S. K., Sato, Y., Kudoh, A., Nakayama, S., Isomura, H., Tsurumi, T. (2007). Enhanced Phosphorylation of Transcription Factor Sp1 in Response to Herpes Simplex Virus Type 1 Infection Is Dependent on the Ataxia Telangiectasia-Mutated Protein. J. Virol. 81: 9653-9664 [Abstract] [Full Text]  
• Luo, M. H., Rosenke, K., Czornak, K., Fortunato, E. A. (2007). Human Cytomegalovirus Disrupts both Ataxia Telangiectasia Mutated Protein (ATM)- and ATM-Rad3-Related Kinase-Mediated DNA Damage Responses during Lytic Infection. J. Virol. 81: 1934-1950 [Abstract] [Full Text]  
• Wilkinson, D. E., Weller, S. K. (2006). Herpes simplex virus type I disrupts the ATR-dependent DNA-damage response during lytic infection. J. Cell Sci. 119: 2695-2703 [Abstract] [Full Text]  
• Stallings, C. L., Duigou, G. J., Gershon, A. A., Gershon, M. D., Silverstein, S. J. (2006). The Cellular Localization Pattern of Varicella-Zoster Virus ORF29p Is Influenced by Proteasome-Mediated Degradation. J. Virol. 80: 1497-1512 [Abstract] [Full Text]  
• Hadjipanayis, C. G., DeLuca, N. A. (2005). Inhibition of DNA Repair by a Herpes Simplex Virus Vector Enhances the Radiosensitivity of Human Glioblastoma Cells. Cancer Res. 65: 5310-5316 [Abstract] [Full Text]  
• Kim, S. K., Albrecht, R. A., O'Callaghan, D. J. (2004). A Negative Regulatory Element (Base Pairs -204 to -177) of the EICP0 Promoter of Equine Herpesvirus 1 Abolishes the EICP0 Protein's trans-Activation of Its Own Promoter. J. Virol. 78: 11696-11706 [Abstract] [Full Text]  
• Melroe, G. T., DeLuca, N. A., Knipe, D. M. (2004). Herpes Simplex Virus 1 Has Multiple Mechanisms for Blocking Virus-Induced Interferon Production. J. Virol. 78: 8411-8420 [Abstract] [Full Text]  
• Boutell, C., Everett, R. D. (2004). Herpes Simplex Virus Type 1 Infection Induces the Stabilization of p53 in a USP7- and ATM-Independent Manner. J. Virol. 78: 8068-8077 [Abstract] [Full Text]  
• Graham, K. L., Gustin, K. E., Rivera, C., Kuyumcu-Martinez, N. M., Choe, S. S., Lloyd, R. E., Sarnow, P., Utz, P. J. (2004). Proteolytic Cleavage of the Catalytic Subunit of DNA-Dependent Protein Kinase during Poliovirus Infection. J. Virol. 78: 6313-6321 [Abstract] [Full Text]  
• Taylor, T. J., Knipe, D. M. (2004). Proteomics of Herpes Simplex Virus Replication Compartments: Association of Cellular DNA Replication, Repair, Recombination, and Chromatin Remodeling Proteins with ICP8. J. Virol. 78: 5856-5866 [Abstract] [Full Text]  
• Wilkinson, D. E., Weller, S. K. (2004). Recruitment of Cellular Recombination and Repair Proteins to Sites of Herpes Simplex Virus Type 1 DNA Replication Is Dependent on the Composition of Viral Proteins within Prereplicative Sites and Correlates with the Induction of the DNA Damage Response. J. Virol. 78: 4783-4796 [Abstract] [Full Text]  
• Hagglund, R., Roizman, B. (2004). Role of ICP0 in the Strategy of Conquest of the Host Cell by Herpes Simplex Virus 1. J. Virol. 78: 2169-2178 [Full Text]  
• Lin, R., Noyce, R. S., Collins, S. E., Everett, R. D., Mossman, K. L. (2004). The Herpes Simplex Virus ICP0 RING Finger Domain Inhibits IRF3- and IRF7-Mediated Activation of Interferon-Stimulated Genes. J. Virol. 78: 1675-1684 [Abstract] [Full Text]  
• Hagglund, R., Roizman, B. (2003). Herpes Simplex Virus 1 Mutant in Which the ICP0 HUL-1 E3 Ubiquitin Ligase Site Is Disrupted Stabilizes cdc34 but Degrades D-Type Cyclins and Exhibits Diminished Neurotoxicity. J. Virol. 77: 13194-13202 [Abstract] [Full Text]  
• Davido, D. J., von Zagorski, W. F., Maul, G. G., Schaffer, P. A. (2003). The Differential Requirement for Cyclin-Dependent Kinase Activities Distinguishes Two Functions of Herpes Simplex Virus Type 1 ICP0. J. Virol. 77: 12603-12616 [Abstract] [Full Text]  
• Sandri-Goldin, R. M. (2003). Replication of the herpes simplex virus genome: Does it really go around in circles?. Proc. Natl. Acad. Sci. USA 100: 7428-7429 [Full Text]  
• Jackson, S. A., DeLuca, N. A. (2003). Relationship of herpes simplex virus genome configuration to productive and persistent infections. Proc. Natl. Acad. Sci. USA 100: 7871-7876 [Abstract] [Full Text]  
• Geiser, V., Jones, C. (2003). Stimulation of bovine herpesvirus-1 productive infection by the adenovirus E1A gene and a cell cycle regulatory gene, E2F-4. J. Gen. Virol. 84: 929-938 [Abstract] [Full Text]  
• Collis, S. J., Swartz, M. J., Nelson, W. G., DeWeese, T. L. (2003). Enhanced Radiation and Chemotherapy-mediated Cell Killing of Human Cancer Cells by Small Inhibitory RNA Silencing of DNA Repair Factors. Cancer Res. 63: 1550-1554 [Abstract] [Full Text]  
• Kim, S. K., Jang, H. K., Albrecht, R. A., Derbigny, W. A., Zhang, Y., O'Callaghan, D. J. (2003). Interaction of the Equine Herpesvirus 1 EICP0 Protein with the Immediate-Early (IE) Protein, TFIIB, and TBP May Mediate the Antagonism between the IE and EICP0 Proteins. J. Virol. 77: 2675-2685 [Abstract] [Full Text]  
• Hagglund, R., Van Sant, C., Lopez, P., Roizman, B. (2002). Herpes simplex virus 1-infected cell protein 0 contains two E3 ubiquitin ligase sites specific for different E2 ubiquitin-conjugating enzymes. Proc. Natl. Acad. Sci. USA 99: 631-636 [Abstract] [Full Text]  
• Zhang, Y., Jones, C. (2001). The Bovine Herpesvirus 1 Immediate-Early Protein (bICP0) Associates with Histone Deacetylase 1 To Activate Transcription. J. Virol. 75: 9571-9578 [Abstract] [Full Text]  
• Van Sant, C., Hagglund, R., Lopez, P., Roizman, B. (2001). The infected cell protein 0 of herpes simplex virus 1 dynamically interacts with proteasomes, binds and activates the cdc34 E2 ubiquitin-conjugating enzyme, and possesses in vitro E3 ubiquitin ligase activity. Proc. Natl. Acad. Sci. USA 10.1073/pnas.161283098v1 [Abstract] [Full Text]  
• Parkinson, J., Everett, R. D. (2001). Alphaherpesvirus Proteins Related to Herpes Simplex Virus Type 1 ICP0 Induce the Formation of Colocalizing, Conjugated Ubiquitin. J. Virol. 75: 5357-5362 [Abstract] [Full Text]  
• Hobbs, W. E., Brough, D. E., Kovesdi, I., DeLuca, N. A. (2001). Efficient Activation of Viral Genomes by Levels of Herpes Simplex Virus ICP0 Insufficient To Affect Cellular Gene Expression or Cell Survival. J. Virol. 75: 3391-3403 [Abstract] [Full Text]  
• Van Sant, C., Lopez, P., Advani, S. J., Roizman, B. (2001). Role of Cyclin D3 in the Biology of Herpes Simplex Virus 1 ICP0. J. Virol. 75: 1888-1898 [Abstract] [Full Text]  
• Kawaguchi, Y., Tanaka, M., Yokoymama, A., Matsuda, G., Kato, K., Kagawa, H., Hirai, K., Roizman, B. (2001). Herpes simplex virus 1 alpha regulatory protein ICP0 functionally interacts with cellular transcription factor BMAL1. Proc. Natl. Acad. Sci. USA 10.1073/pnas.041592598v1 [Abstract] [Full Text]  
• Parkinson, J., Everett, R. D. (2000). Alphaherpesvirus Proteins Related to Herpes Simplex Virus Type 1 ICP0 Affect Cellular Structures and Proteins. J. Virol. 74: 10006-10017 [Abstract] [Full Text]  
• Mossman, K. L., Smiley, J. R. (1999). Truncation of the C-Terminal Acidic Transcriptional Activation Domain of Herpes Simplex Virus VP16 Renders Expression of the Immediate-Early Genes Almost Entirely Dependent on ICP0. J. Virol. 73: 9726-9733 [Abstract] [Full Text]  
• Lomonte, P., Everett, R. D. (1999). Herpes Simplex Virus Type 1 Immediate-Early Protein Vmw110 Inhibits Progression of Cells through Mitosis and from G1 into S Phase of the Cell Cycle. J. Virol. 73: 9456-9467 [Abstract] [Full Text]  
• Hobbs, W. E. II, DeLuca, N. A. (1999). Perturbation of Cell Cycle Progression and Cellular Gene Expression as a Function of Herpes Simplex Virus ICP0. J. Virol. 73: 8245-8255 [Abstract] [Full Text]  
• Smith, G. C.M., Jackson, S. P. (1999). The DNA-dependent protein kinase. Genes Dev. 13: 916-934 [Full Text]  
• Leib, D. A., Harrison, T. E., Laslo, K. M., Machalek, M. A., Moorman, N. J., Virgin, H. W. (1999). Interferons Regulate the Phenotype of  Wild-type and Mutant Herpes Simplex Viruses In Vivo. J. Exp. Med. 189: 663-672 [Abstract] [Full Text]  
• Everett, R. D., Meredith, M., Orr, A. (1999). The Ability of Herpes Simplex Virus Type 1 Immediate-Early Protein Vmw110 To Bind to a Ubiquitin-Specific Protease Contributes to Its Roles in the Activation of Gene Expression and Stimulation of Virus Replication. J. Virol. 73: 417-426 [Abstract] [Full Text]  
• Parkinson, J., Lees-Miller, S. P., Everett, R. D. (1999). Herpes Simplex Virus Type 1 Immediate-Early Protein Vmw110 Induces the Proteasome-Dependent Degradation of the Catalytic Subunit of DNA-Dependent Protein Kinase. J. Virol. 73: 650-657 [Abstract] [Full Text]  
• Burkham, J., Coen, D. M., Weller, S. K. (1998). ND10 Protein PML Is Recruited to Herpes Simplex Virus Type 1 Prereplicative Sites and Replication Compartments in the Presence of Viral DNA Polymerase. J. Virol. 72: 10100-10107 [Abstract] [Full Text]  
• Smith, C. C., Peng, T., Kulka, M., Aurelian, L. (1998). The PK Domain of the Large Subunit of Herpes Simplex Virus Type 2 Ribonucleotide Reductase (ICP10) Is Required for Immediate-Early Gene Expression and Virus Growth. J. Virol. 72: 9131-9141 [Abstract] [Full Text]  
• Lium, E. K., Panagiotidis, C. A., Wen, X., Silverstein, S. J. (1998). The NH2 Terminus of the Herpes Simplex Virus Type 1 Regulatory Protein ICP0 Contains a Promoter-Specific Transcription Activation Domain. J. Virol. 72: 7785-7795 [Abstract] [Full Text]  
• Petroski, M. D., Wagner, E. K. (1998). Purification and Characterization of a Cellular Protein That Binds to the Downstream Activation Sequence of the Strict Late UL38 Promoter of Herpes Simplex Virus Type 1. J. Virol. 72: 8181-8190 [Abstract] [Full Text]  
• Everett, R. D., Freemont, P., Saitoh, H., Dasso, M., Orr, A., Kathoria, M., Parkinson, J. (1998). The Disruption of ND10 during Herpes Simplex Virus Infection Correlates with the Vmw110- and Proteasome-Dependent Loss of Several PML Isoforms. J. Virol. 72: 6581-6591 [Abstract] [Full Text]  
• Jordan, R., Pepe, J., Schaffer, P. A. (1998). Characterization of a Nerve Growth Factor-Inducible Cellular Activity That Enhances Herpes Simplex Virus Type 1 Gene Expression and Replication of an ICP0 Null Mutant in Cells of Neural Lineage. J. Virol. 72: 5373-5382 [Abstract] [Full Text]  
• Samaniego, L. A., Neiderhiser, L., DeLuca, N. A. (1998). Persistence and Expression of the Herpes Simplex Virus Genome in the Absence of Immediate-Early Proteins. J. Virol. 72: 3307-3320 [Abstract] [Full Text]  
• Kawaguchi, Y., Tanaka, M., Yokoymama, A., Matsuda, G., Kato, K., Kagawa, H., Hirai, K., Roizman, B. (2001). Herpes simplex virus 1 alpha regulatory protein ICP0 functionally interacts with cellular transcription factor BMAL1. Proc. Natl. Acad. Sci. USA 98: 1877-1882 [Abstract] [Full Text]  
• Van Sant, C., Hagglund, R., Lopez, P., Roizman, B. (2001). The infected cell protein 0 of herpes simplex virus 1 dynamically interacts with proteasomes, binds and activates the cdc34 E2 ubiquitin-conjugating enzyme, and possesses in vitro E3 ubiquitin ligase activity. Proc. Natl. Acad. Sci. USA 98: 8815-8820 [Abstract] [Full Text]