CT-1 and Oct-2 DNA-binding site specificity is regulated <i>in vitro</i> by different kinases

Grenfell, S. J.; Latchman, David S.; Thomas, Nancy

doi:10.1042/bj3170959c

Cited by 6 publications

(6 citation statements)

References 31 publications

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“…8, arrowhead). Finally, oct-1 activity is also regulated by phosphorylation (21), and cdks may be among the protein kinases that phosphorylate oct-1 (47). In addition to the four factors which are essential for IE transcription (VP16, HCF, oct-1, and the cellular transcription complex), ICP0, an HSV IE regulatory protein, is further required to achieve wild-type levels of IE gene transcription.…”

Section: Discussionmentioning

confidence: 99%

Requirement for Cellular Cyclin-Dependent Kinases in Herpes Simplex Virus Replication and Transcription

Schang

Schaffer

1998

J Virol

145

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Several observations indicate that late-G1/S-phase-specific cellular functions may be required for herpes simplex virus (HSV) replication: (i) certain mutant HSV strains are replication impaired during infection of cells in the G0/G1 but not in the G1/S phase of the cell cycle, (ii) several late-G1/S-phase-specific cellular proteins and functions are induced during infection, and (iii) the activity of a cellular protein essential for expression of viral immediate-early (IE) genes, HCF, is normally required during the late G1/S phase of the cell cycle. To test the hypothesis that late-G1/S-phase-specific cellular functions are necessary for HSV replication, HEL or Vero cells were infected in the presence of the cell cycle inhibitors roscovitine (Rosco) and olomoucine (Olo). Both drugs inhibit cyclin-dependent kinase 1 (cdk-1) and cdk-2 (required for cell cycle progression into the late G1/S phase) and cdk-5 (inactive in cycling cells) but not cdk-4 or cdk-6 (active at early G1). We found that HSV replication was inhibited by Rosco and Olo but not by lovastatin (a cell cycle inhibitor that does not inhibit cdk activity), staurosporine (a broad-spectrum protein serine-threonine kinase inhibitor), PD98059 (an inhibitor specific for erk-1 and -2) or iso-Olo (a structural isomer of Olo that does not inhibit cdk activity). The concentrations of Rosco and Olo required to inhibit cell cycle progression and viral replication in both HEL and Vero cells were similar. Inhibition of viral replication was found not to be mediated by drug-induced cytotoxicity. Efforts to isolate Rosco- or Olo-resistant HSV mutants were unsuccessful, indicating that these drugs do not act by inhibiting a single viral target. Viral DNA replication and accumulation of IE and early viral RNAs were inhibited in the presence of cell cycle-inhibitory concentrations of Rosco or Olo. We therefore conclude that one or more cdks active from late G1 onward or inactive in nonneuronal cells are required for accumulation of HSV transcripts, viral DNA replication, and production of infectious virus.

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Section: Discussionmentioning

confidence: 99%

Requirement for Cellular Cyclin-Dependent Kinases in Herpes Simplex Virus Replication and Transcription

Schang

Schaffer

1998

J Virol

145

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“…Like other transcription factors, Western blotting and immunoprecipitation analyses revealed that the phosphorylation/dephosphorylation of Oct-1 is a common mechanism that regulates the binding of itself to octamer motifs and the activation of target gene transcription. Previous studies have shown that Oct-1 is phosphorylated in cellcycle-dependent, cell-type-dependent, protein kinase-dependent and sequence-dependent manners [23]. For instance, PKA (protein kinase A)-mediated phosphorylation of Oct-1 inhibits its DNA-binding activity, while PKC-and CK2 (protein kinase CK2)-mediated phosphorylation of Oct-1 enhances its DNAbinding activity [23].…”

Section: Central Role Of Oct-1 In Ox-ldl-induced Lox-1 Promoter Activmentioning

confidence: 99%

“…Previous studies have shown that Oct-1 is phosphorylated in cellcycle-dependent, cell-type-dependent, protein kinase-dependent and sequence-dependent manners [23]. For instance, PKA (protein kinase A)-mediated phosphorylation of Oct-1 inhibits its DNA-binding activity, while PKC-and CK2 (protein kinase CK2)-mediated phosphorylation of Oct-1 enhances its DNAbinding activity [23]. Furthermore, in addition to protein kinases, oxidation/reduction might be another mechanism whereby the phosphorylation of Oct-1 and Oct-1-mediated transcription of a specific gene is regulated [23].…”

Section: Central Role Of Oct-1 In Ox-ldl-induced Lox-1 Promoter Activmentioning

confidence: 99%

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) transcriptional regulation by Oct-1 in human endothelial cells: implications for atherosclerosis

Chen

Liu

et al. 2005

Biochemical Journal

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LOX-1, a receptor for ox-LDL (oxidized low-density lipoprotein), has recently been determined to play a critical role in the progression of atherosclerosis. LOX-1 expression (mRNA and protein) has been shown to be up-regulated by pro-atherogenic stimuli, such as ox-LDL and Ang II (angiotensin II). However, the molecular mechanisms of these up-regulations are unclear. In the present study, we explored LOX-1 transcriptional promoter activation in response to ox-LDL and Ang II. Under basal states, LOX-1 core promoter (LOX-1 -35/+36) was found to be sufficient for its basal activity in HCAECs (human coronary artery endothelial cells). More importantly, we found that ox-LDL (60 microg/ml for 24 h) induced LOX-1 promoter activity significantly and that a 105 bp fragment (between nt -1599 and -1494) was required for this activation. Within this 106 bp fragment, there is a potential binding motif for the transcription factor Oct-1 (octamer-1). By electrophoretic mobility-shift assay, we observed the activation of Oct-1 by ox-LDL. The critical role of Oct-1 in ox-LDL-induced LOX-1 promoter activation was further confirmed by mutagenesis assay. For comparison, we also examined LOX-1 promoter activation in response to Ang II (1 micromol/l for 24 h). Interestingly, another promoter region, between nt -2336 and -1990, was required for Ang II-induced LOX-1 promoter activation. In conclusion, the present study strongly suggests that ox-LDL, by activating Oct-1, induces LOX-1 promoter activation. Furthermore, this study suggests that while ox-LDL and Ang II both induce LOX-1 expression in HCAECs, the underlying mechanisms of promoter activation are different from each other.

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“…Since cdks are involved in regulating the activities of specific cellular transcription factors (reviewed in reference 9), phosphorylation of these cellular factors could explain the requirement of HSV transcription for cdks. For instance, the activity of oct-1, which is required for HSV IE gene expression, is regulated by cdk phosphorylation (19,53). Other cellular transcription factors, including E2F, are further regulated by cdk-2 through more complex mechanisms (2,10,12,32,43,45,52,66).…”

Section: Discussionmentioning

confidence: 99%

Transcription of Herpes Simplex Virus Immediate-Early and Early Genes Is Inhibited by Roscovitine, an Inhibitor Specific for Cellular Cyclin-Dependent Kinases

Schang

Rosenberg

Schaffer

1999

J Virol

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Although herpes simplex virus (HSV) replicates in noncycling as well as cycling cells, including terminally differentiated neurons, it has recently been shown that viral replication requires the activities of cellular cyclin-dependent kinases (cdks) (L. M. Schang, J. Phillips, and P. A. Schaffer, J. Virol. 72:5626–5637, 1998). Since we were unable to isolate HSV mutants resistant to two cdk inhibitors, Olomoucine and Roscovitine (Rosco), we hypothesized that cdks may be required for more than one viral function during HSV replication. In the experiments presented here, we tested this hypothesis by measuring the efficiency of (i) viral replication; (ii) expression of selected immediate-early (IE) (ICP0 and ICP4), early (E) (ICP8 and TK), and late (L) (gC) genes; and (iii) viral DNA synthesis in infected cultures to which Rosco was added after IE or IE and E proteins had already been synthesized. Rosco inhibited HSV replication, transcription of IE and E genes, and viral DNA synthesis when added at 1, 2, or 6 h postinfection or after release from a 6-h cycloheximide block. Transcription of a representative L gene, gC, was also inhibited by Rosco under all conditions examined. We conclude from these studies that cellular cdks are required for transcription of E as well as IE genes. In contrast, steady-state levels of at least one cellular housekeeping gene were not affected by Rosco. The requirement of viral IE and E transcription for cellular cdks may reflect either a requirement for specific cdk-activated cellular and/or viral transcription factors or a more global requirement for cdks in the transcriptional activation of the viral genome.

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CT-1 and Oct-2 DNA-binding site specificity is regulated in vitro by different kinases

Cited by 6 publications

References 31 publications

Requirement for Cellular Cyclin-Dependent Kinases in Herpes Simplex Virus Replication and Transcription

Requirement for Cellular Cyclin-Dependent Kinases in Herpes Simplex Virus Replication and Transcription

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) transcriptional regulation by Oct-1 in human endothelial cells: implications for atherosclerosis

Transcription of Herpes Simplex Virus Immediate-Early and Early Genes Is Inhibited by Roscovitine, an Inhibitor Specific for Cellular Cyclin-Dependent Kinases

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