The Host-Cell Architectural Protein HMG I(Y) Modulates Binding of Herpes Simplex Virus Type 1 ICP4 to Its Cognate Promoter

Panagiotidis, Christos Α.; Silverstein, Saul

doi:10.1006/viro.1999.9607

Cited by 16 publications

(12 citation statements)

References 87 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3B is that repression of the LAT promoter by ICP4 is a stoichiometric process in which the rate-limiting step is formation of a stable complex between ICP4 and a high-affinity ICP4 binding site that spans the LAT promoter (1,41). This interpretation is consistent with the finding that a cellular protein (HMG1) which augments binding of ICP4 to DNA also enhances repression by ICP4 in transient-transfection assays (37).…”

Section: Discussionsupporting

confidence: 67%

Identification of a Motif in the C Terminus of Herpes Simplex Virus Regulatory Protein ICP4 That Contributes to Activation of Transcription

Bruce

Wilcox

2002

J Virol

View full text Add to dashboard Cite

Expression of most viral genes during productive infection by herpes simplex virus is regulated by the viral protein ICP4 (also called IE175 or Vmw175). The N-terminal portion of ICP4 contains well-defined transactivation, DNA binding, and dimerization domains that contribute to promoter regulation. The C-terminal half of ICP4 contributes to the activity of ICP4, but the functional motifs have not been well mapped. To localize functional motifs in the C-terminal half of ICP4, we have compared the relative specific activities of ICP4 variants in transient-transfection assays. Deletion of the C-terminal 56 residues reduces the specific activity more than 10-fold. Mutational analysis identified three consecutive residues (1252 to 1254) that are conserved in ICP4 orthologs and are essential for full activity, especially in the context of ICP4 variants with a deletion in the N-terminal transactivation domain. Recombinant viruses that encode variants of ICP4 with mutations in the N-terminal transactivation domain and/or the extreme C terminus were constructed. The phenotypes of these recombinant viruses support the hypothesis that efficient promoter activation by ICP4 requires motifs at both the N and C termini. The data suggest that the C terminus of ICP4 functions not as an independent transactivation domain but as an enhancer of the ICP4 N-terminal transactivation domain. The data provide further support for the hypothesis that some ICP4 motifs required for promoter activation are not required for promoter repression and suggest that ICP4 utilizes different cellular factors for activation or repression of viral promoters.During productive infection by herpes simplex virus type 1 (HSV-1), approximately 75 genes encoded within the linear 152-kbp viral genome are transcribed by RNA polymerase II in three sequential phases designated immediate early (IE or ␣), early (E or ␤), and late (L or ␥) (for a review, see reference 52). The immediate-early protein ICP4 (infected-cell polypeptide 4) is required for efficient transcription of early and late viral genes and thus is essential for productive infection. The immediate-early proteins ICP0, ICP22, and ICP27 enhance expression of early and late genes at both transcriptional and posttranscriptional levels and contribute to some functions of ICP4 (52).ICP4 is a 1,298-amino-acid (aa) phosphoprotein that binds DNA in a sequence-specific manner as a homodimer (14,16,17,34). ICP4 represses transcription from three viral genes (LAT, ICP4, and ORF-P) that have a high-affinity ICP4 binding site spanning the transcription initiation site (1,16,20,21,28,30,41,42). ICP4 stimulates transcription from early and late viral promoters through interactions with viral DNA and cellular proteins that are poorly understood. Although the ICP4 DNA binding domain is essential for activation of transcription (39, 45), extensive analyses have not revealed a specific sequence that binds ICP4 with high affinity and is common to all promoters activated by ICP4 (13, 52). The observation that the minima...

show abstract

Section: Discussionsupporting

confidence: 67%

Identification of a Motif in the C Terminus of Herpes Simplex Virus Regulatory Protein ICP4 That Contributes to Activation of Transcription

Bruce

Wilcox

2002

J Virol

View full text Add to dashboard Cite

show abstract

“…Indeed, architectural factors, either from the HMG family, or not (LEF-1 for example), produce topological changes in the DNA (21,52,56) and even looped structures, as shown for the ␤-globin promoter (6). In addition, HMG-I(Y) has been shown to increase binding affinities of several transcription factors (28,31,23,40,56), and we can therefore speculate that it plays such a role in the HPV18 enhanceosome, although more work is needed to determine the other factors involved.…”

Section: Discussionmentioning

confidence: 99%

HMG-I(Y) and the CBP/p300 Coactivator Are Essential for Human Papillomavirus Type 18 Enhanceosome Transcriptional Activity

Bouallaga

Teissier

Yaniv

et al. 2003

Molecular and Cellular Biology

View full text Add to dashboard Cite

“…However, there are no DNA sequences unique to the promoters of all E genes, and many non-HSV-1 promoters recombined into the viral genome are regulated as HSV-1 E promoters (i.e., they require IE proteins) (78,79). Consequently, it is currently accepted that ICP0 and ICP4 activate transcription through indirect mechanisms that operate independently of promoter-specific sequences or transcription factors, which are the subject of intensive research (1,7,18,19,21,22,34,54,60,80). ICP4 also inhibits the expression of IE genes, by binding with high affinity to sequences near their transcription start sites (35).…”

mentioning

confidence: 99%

Roscovitine Inhibits Activation of Promoters in Herpes Simplex Virus Type 1 Genomes Independently of Promoter-Specific Factors

Diwan¹,

Lacasse²,

Schang

2004

J Virol

View full text Add to dashboard Cite

Flavopiridol, roscovitine, and other inhibitors of Cyclin-Dependent Kinases (CDK) inhibit the replication of a variety of viruses in vitro while proving nontoxic in human clinical trials of their effects against cancer. Consequently, these and other Pharmacological CDK inhibitors (PCIs) have been proposed as potential antivirals. Flavopiridol potently inhibits all tested CDKs and inhibits the transcription of most cellular and viral genes. In contrast, roscovitine and other purine PCIs inhibit with high potency only CDK1, CDK2, CDK5, and CDK7, and they specifically inhibit the expression of viral but not cellular genes. The levels at which purine PCIs inhibit gene expression are unknown, as are the factors which determine their specificity for expression of viral but not cellular genes. We show herein that roscovitine prevents the initiation of transcription of herpes simplex virus type 1 (HSV-1) genes but has no effect on transcription elongation. We further show that roscovitine does not inhibit the initiation or elongation of cellular transcription and that its inhibitory effects are specific for promoters in HSV-1 genomes. Therefore, we have identified a novel biological activity for PCIs, i.e., their ability to prevent the initiation of transcription. We have also identified genome location as one of the factors that determine whether the transcription of a given gene is inhibited by roscovitine. The activities of roscovitine on viral transcription resemble one of the antiherpesvirus activities of alpha interferon and could be used as a model for the development of novel antivirals. The genome-specific effects of roscovitine may also be important for its development against virus-induced cancers.

show abstract

The Host-Cell Architectural Protein HMG I(Y) Modulates Binding of Herpes Simplex Virus Type 1 ICP4 to Its Cognate Promoter

Cited by 16 publications

References 87 publications

Identification of a Motif in the C Terminus of Herpes Simplex Virus Regulatory Protein ICP4 That Contributes to Activation of Transcription

Identification of a Motif in the C Terminus of Herpes Simplex Virus Regulatory Protein ICP4 That Contributes to Activation of Transcription

HMG-I(Y) and the CBP/p300 Coactivator Are Essential for Human Papillomavirus Type 18 Enhanceosome Transcriptional Activity

Roscovitine Inhibits Activation of Promoters in Herpes Simplex Virus Type 1 Genomes Independently of Promoter-Specific Factors

Contact Info

Product

Resources

About