scholarly journals Regulation of cyclin E gene expression by the human papillomavirus type 16 E7 oncoprotein

1999 ◽  
Vol 80 (8) ◽  
pp. 2103-2113 ◽  
Author(s):  
Beate Vogt ◽  
Karin Zerfaß-Thome ◽  
Almut Schulze ◽  
Jürgen W. Botz ◽  
Werner Zwerschke ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Transcriptional Activation ◽  
Binding Sites ◽  
Cyclin E ◽  
Regulatory Region ◽  
Regulatory Elements ◽  
E Gene ◽  
Human Papillomavirus Type 16 ◽  
Activation Of Transcription ◽  
Cellular Transcription

In this study, we characterized the 5′ regulatory region of the murine cyclin E gene and analysed activation of the gene by the E7 oncogene of human papillomavirus type 16 in transfection experiments. We found that the murine cyclin E promoter is composed of multiple regulatory elements, and we present evidence for at least two independent transcription units, designated P1 and P2. Overlapping binding sites for the cellular transcription factors Sp1 and E2F were identified in both promoters, and we found that E2F-mediated activation of transcription is inhibited by Sp1 in cotransfection experiments. The E2F/Sp1 binding sites contribute to transcriptional activation by E7, and the data suggest that the cyclin E gene is rendered E7-inducible through the combination of several cis-acting elements which display only weak intrinsic responsiveness to E7.

scholarly journals Transcriptional Activation of the Telomerase hTERT Gene by Human Papillomavirus Type 16 E6 Oncoprotein

2001 ◽  
Vol 75 (9) ◽  
pp. 4467-4472 ◽  
Author(s):  
Tim Veldman ◽  
Izumi Horikawa ◽  
J. Carl Barrett ◽  
Richard Schlegel
Keyword(s):  
Human Papillomavirus ◽  
Transcriptional Activation ◽  
Transcriptional Control ◽  
Regulatory Region ◽  
Rnase Protection ◽  
Hpv 16 ◽  
Htert Gene ◽  
Human Papillomavirus Type 16 ◽  
E6 Gene

ABSTRACT The E6 and E7 oncogenes of human papillomavirus type 16 (HPV-16) are sufficient for the immortalization of human genital keratinocytes in vitro. The products of these viral genes associate with p53 and pRb tumor suppressor proteins, respectively, and interfere with their normal growth-regulatory functions. The HPV-16 E6 protein has also been shown to increase the telomerase enzyme activity in primary epithelial cells by an unknown mechanism. We report here that a study using reverse transcription-PCR and RNase protection assays in transduced primary human foreskin keratinocytes (HFKs) shows that the E6 gene (but not the E7 gene) increases telomerase hTERT gene transcription coordinately with E6-induced telomerase activity. In these same cells, the E6 gene induces a 6.5-fold increase in the activity of a 1,165-bp 5′ promoter/regulatory region of the hTERT gene, and this induction is attributable to a minimal 251-bp sequence (−211 to +40). Furthermore, there is a 35-bp region (+5 to +40) within this minimal E6-responsive promoter that is responsible for 60% of E6 activity. Although the minimal hTERT promoter contains Myc-responsive E-box elements and recent studies have suggested a role for Myc protein in hTERT transcriptional control, we found no alterations in the abundance of either c-Myc or c-Mad in E6-transduced HFKs, suggesting that there are other or additional transcription factors critical for regulating hTERT expression.

scholarly journals Multiple ASF/SF2 Sites in the Human Papillomavirus Type 16 (HPV-16) E4-Coding Region Promote Splicing to the Most Commonly Used 3′-Splice Site on the HPV-16 Genome

2010 ◽  
Vol 84 (16) ◽  
pp. 8219-8230 ◽  
Author(s):  
Monika Somberg ◽  
Stefan Schwartz
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Splice Site ◽  
Binding Sites ◽  
Mrna Levels ◽  
Coding Region ◽  
Cervical Lesions ◽  
Hpv 16 ◽  
Human Papillomavirus Type 16 ◽  
E6 And E7

ABSTRACT Our results presented here demonstrate that the most abundant human papillomavirus type 16 (HPV-16) mRNAs expressing the viral oncogenes E6 and E7 are regulated by cellular ASF/SF2, itself defined as a proto-oncogene and overexpressed in cervical cancer cells. We show that the most frequently used 3′-splice site on the HPV-16 genome, site SA3358, which is used to produce primarily E4, E6, and E7 mRNAs, is regulated by ASF/SF2. Splice site SA3358 is immediately followed by 15 potential binding sites for the splicing factor ASF/SF2. Recombinant ASF/SF2 binds to the cluster of ASF/SF2 sites. Mutational inactivation of all 15 sites abolished splicing to SA3358 and redirected splicing to the downstream-located, late 3′-splice site SA5639. Overexpression of a mutant ASF/SF2 protein that lacks the RS domain, also totally inhibited the usage of SA3358 and redirected splicing to the late 3′-splice site SA5639. The 15 ASF/SF2 binding sites could be replaced by an ASF/SF2-dependent, HIV-1-derived splicing enhancer named GAR. This enhancer was also inhibited by the mutant ASF/SF2 protein that lacks the RS domain. Finally, silencer RNA (siRNA)-mediated knockdown of ASF/SF2 caused a reduction in spliced HPV-16 mRNA levels. Taken together, our results demonstrate that the major HPV-16 3′-splice site SA3358 is dependent on ASF/SF2. SA3358 is used by the most abundantly expressed HPV-16 mRNAs, including those encoding E6 and E7. High levels of ASF/SF2 may therefore be a requirement for progression to cervical cancer. This is supported by our earlier findings that ASF/SF2 is overexpressed in high-grade cervical lesions and cervical cancer.

Analysis of the human CD10/neutral endopeptidase 24.11 promoter region: two separate regulatory elements

Blood ◽  
1995 ◽  
Vol 85 (11) ◽  
pp. 3199-3207 ◽  
Author(s):  
F Ishimaru ◽  
MA Shipp
Keyword(s):  
Binding Sites ◽  
Lymphoblastic Leukemia ◽  
Regulatory Region ◽  
Neutral Endopeptidase ◽  
Regulatory Elements ◽  
Control Element ◽  
Regulatory Regions ◽  
Endopeptidase 24.11

The cell surface zinc metalloproteinase CD10/neutral endopeptidase 24.11 (NEP) is expressed on normal and malignant lymphoid progenitors, granulocytes, and a variety of epithelial cells. To further define the tissue-specific and developmentally related expression of CD10/NEP, we have characterized two separate regulatory regions that control the transcription of 5′ alternatively spliced CD10/NEP transcripts. These type 1 and 2 CD10/NEP regulatory regions are both characterized by the presence of multiple transcription initiation sites and the absence of classic TATA boxes and consensus initiator elements. The purine-rich type 1 regulatory region, which includes 5′ UTR exon 1 sequence, is characterized by multiple putative PU.1 binding sites and consensus ets-binding motifs. In marked contrast, the GC-rich type 2 regulatory region contains multiple putative Sp1 binding sites, a potential consensus retinoblastoma control element (RCE), and an inverted CCAAT box. In the majority of tissues examined to date, type 2 CD10/NEP transcripts were more abundant; the abundance of type 1 transcripts was more variable, with the highest type 1 levels in fetal thymus and certain lymphoblastic leukemia cell lines.

scholarly journals Genetic Analysis of cis Regulatory Elements within the 5′ Region of the Human Papillomavirus Type 31 Upstream Regulatory Region during Different Stages of the Viral Life Cycle

2002 ◽  
Vol 76 (10) ◽  
pp. 4798-4809 ◽  
Author(s):  
Ellora Sen ◽  
Jennifer L. Bromberg-White ◽  
Craig Meyers
Keyword(s):  
Human Papillomavirus ◽  
Life Cycle ◽  
Mutational Analysis ◽  
Regulatory Region ◽  
Regulatory Elements ◽  
Viral Life Cycle ◽  
Viral Gene ◽  
Upstream Regulatory Region ◽  
Kinase C

ABSTRACT The function of the 5′ region of the upstream regulatory region (URR) in regulating E6/E7 expression in cancer-associated papillomaviruses has been largely uncharacterized. In this study we used linker-scanning mutational analysis to identify potential cis regulatory elements contained within a portion of the 5′ region of the URR that are involved in regulating transcription of the E6/E7 promoter at different stages of the viral life cycle. The mutational analysis illustrated differences in the transcriptional utilization of specific regions of the URR depending on the stage of the viral life cycle. This study identified (i) viral cis elements that regulate transcription in the presence and absence of any viral gene products or viral DNA replication, (ii) the role of host tissue differentiation in viral transcriptional regulation, and (iii) cis regulatory regions that are effected by induction of the protein kinase C pathway. Our studies have provided an extensive map of functional elements in the 5′ region (nuncleotides 7259 to 7510) of the human papillomavirus type 31 URR that are involved in the regulation of p99 promoter activity at different stages of the viral life cycle.

The replication activation potential of selected RNA polymerase II promoter elements at the simian virus 40 origin

1992 ◽  
Vol 12 (7) ◽  
pp. 3087-3093
Author(s):  
A T Hoang ◽  
W Wang ◽  
J D Gralla
Keyword(s):  
Rna Polymerase Ii ◽  
Transcriptional Activation ◽  
Binding Sites ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Cos Cells ◽  
Activation Potential ◽  
Multiple Copies ◽  
Cellular Transcription ◽  
Transcriptional Stimulation

Binding sites for cellular transcription factors were placed near the simian virus 40 origin of replication, and their effect on replication and TATA-dependent transcription was measured in COS cells. The hierarchy of transcriptional stimulation changed when the plasmids replicated. Only one of seven inserted sequences, a moderately weak transcription element, stimulated replication detectably. However, when two nonstimulatory sites were present in multiple copies they did activate replication. Multiple sites for the chimeric activator GAL4-VP16 did not stimulate replication even though transcription was stimulated strongly. The results indicate that the ability of a binding site to stimulate replication from the simian virus 40 ori is not based on its transcriptional activation potential but is instead related to a separate replication activation potential that can be increased by having multiple sites.

Identification of cis-regulatory elements in the upstream regulatory region of human papillomavirus type 59

1997 ◽  
Vol 47 (2) ◽  
pp. 155-166 ◽  
Author(s):  
Jaerang Rho ◽  
Soyoung Lee ◽  
Ethel-Michele de Villiers ◽  
Joonho Choe
Keyword(s):  
Human Papillomavirus ◽  
Regulatory Region ◽  
Regulatory Elements ◽  
Upstream Regulatory Region
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