Identification of a novel constitutive enhancer element and an associated binding protein: implications for human papillomavirus type 11 enhancer regulation.

We have identified a cellular enhancer-binding protein, present in nuclear extracts prepared from human and rodent cells, that binds to the adenovirus E1A enhancer element I sequence. The factor has been termed EF-1A, for enhancer-binding factor to the E1A core motif. EF-1A was found to bind to two adjacent, related sequence motifs in the E1A enhancer region (termed sites A and B). The binding of EF-1A to these adjacent sites, or to synthetic dimerized sites of either motif, was cooperative. The cooperative binding of EF-1A to these sites was not subject to strict spacing constraints. EF-1A also bound to related sequences upstream of the E1A enhancer region and in the polyomavirus and adenovirus E4 enhancer regions. The EF-1A-binding region in the E1A enhancer stimulated expression of a linked gene in human 293 cells when multimerized. Based on the contact sites for EF-1A binding determined by chemical interference assays, this protein appears to be distinct from any previously characterized nuclear binding protein.

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Adeno-Associated Virus Major Rep78 Protein Disrupts Binding of TATA-Binding Protein to the p97 Promoter of Human Papillomavirus Type 16

Journal of Virology ◽

10.1128/jvi.74.5.2459-2465.2000 ◽

2000 ◽

Vol 74 (5) ◽

pp. 2459-2465 ◽

Cited By ~ 17

Author(s):

Pei-Fen Su ◽

Shu-Yuan Chiang ◽

Cheng-Wen Wu ◽

Felicia Y.-H. Wu

Keyword(s):

Human Papillomavirus ◽

Binding Protein ◽

Core Promoter ◽

Tata Binding Protein ◽

Tata Box ◽

Dependent Manner ◽

Hpv 16 ◽

Adeno Associated Virus ◽

Human Papillomavirus Type 16 ◽

E6 And E7

ABSTRACT Adeno-associated virus type 2 (AAV) is known to inhibit the promoter activities of several oncogenes and viral genes, including the human papillomavirus type 16 (HPV-16) E6 and E7 transforming genes. However, the target elements of AAV on the long control region (LCR) upstream of E6 and E7 oncogenes are elusive. A chloramphenicol acetyltransferase assay was performed to study the effect of AAV on the transcription activity of the HPV-16 LCR in SiHa (HPV-positive) and C-33A (HPV-negative) cells. The results reveal that (i) AAV inhibited HPV-16 LCR activity in a dose-dependent manner, (ii) AAV-mediated inhibition did not require the HPV gene products, and (iii) the AAV replication gene product Rep78 was involved in the inhibition. Deletion mutation analyses of the HPV-16 LCR showed that regulatory elements outside the core promoter region of the LCR may not be direct targets of AAV-mediated inhibition. Further study with the electrophoretic mobility shift assay demonstrated that Rep78 interfered with the binding of TATA-binding protein (TBP) to the TATA box of the p97 core promoter more significantly than it disrupted the preformed TBP-TATA complex. These data thus suggest that Rep78 may inhibit transcription initiation of the HPV-16 LCR by disrupting the interaction between TBP and the TATA box of the p97 core promoter.

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Human Papillomavirus E7 Oncoprotein Increases Production of the Anti-Inflammatory Interleukin-18 Binding Protein in Keratinocytes

Journal of Virology ◽

10.1128/jvi.02546-13 ◽

2014 ◽

Vol 88 (8) ◽

pp. 4173-4179 ◽

Cited By ~ 14

Author(s):

K. H. Richards ◽

R. Doble ◽

C. W. Wasson ◽

M. Haider ◽

G. E. Blair ◽

...

Keyword(s):

Human Papillomavirus ◽

Binding Protein ◽

Interleukin 18 ◽

E7 Oncoprotein ◽

Anti Inflammatory

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Human papillomavirus (HPV) origin-binding protein associates with mitotic spindles to enable viral DNA partitioning

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0306848101 ◽

2004 ◽

Vol 101 (12) ◽

pp. 4030-4035 ◽

Cited By ~ 68

Author(s):

B. A. Van Tine ◽

L. D. Dao ◽

S.-Y. Wu ◽

T. M. Sonbuchner ◽

B. Y. Lin ◽

...

Keyword(s):

Human Papillomavirus ◽

Binding Protein ◽

Mitotic Spindles ◽

Viral Dna ◽

Origin Binding Protein ◽

Dna Partitioning

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Abstract LB-112: The human papillomavirus type 16 E5 protein represses X-box binding protein 1 and cyclooxygenase-2 stress signaling in keratinocytes

10.1158/1538-7445.am10-lb-112 ◽

2010 ◽

Author(s):

Sawali R. Sudarshan ◽

Xuefeng Liu ◽

Richard Schlegel

Keyword(s):

Human Papillomavirus ◽

Binding Protein ◽

Cyclooxygenase 2 ◽

Stress Signaling ◽

Human Papillomavirus Type 16 ◽

E5 Protein

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Human Papillomavirus Type 16 E7 Oncoprotein Binds and Inactivates Growth-Inhibitory Insulin-Like Growth Factor Binding Protein 3

Molecular and Cellular Biology ◽

10.1128/.20.17.6483-6495.2000 ◽

2000 ◽

Vol 20 (17) ◽

pp. 6483-6495

Author(s):

Boris Mannhardt ◽

Stuart A. Weinzimer ◽

Mechthild Wagner ◽

Marc Fiedler ◽

Pinchas Cohen ◽

...

Keyword(s):

Human Papillomavirus ◽

Growth Factor ◽

Binding Protein ◽

Insulin Like Growth Factor ◽

Factor Binding ◽

E7 Oncoprotein ◽

Human Papillomavirus Type 16 ◽

Growth Inhibitory

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Dynamic Localization of the Human Papillomavirus Type 11 Origin Binding Protein E2 through Mitosis While in Association with the Spindle Apparatus

Journal of Virology ◽

10.1128/jvi.80.10.4792-4800.2006 ◽

2006 ◽

Vol 80 (10) ◽

pp. 4792-4800 ◽

Cited By ~ 29

Author(s):

Luan D. Dao ◽

Aaron Duffy ◽

Brian A. Van Tine ◽

Shwu-Yuan Wu ◽

Cheng-Ming Chiang ◽

...

Keyword(s):

Human Papillomavirus ◽

Binding Protein ◽

Cellular Protein ◽

Bovine Papillomavirus ◽

Mitotic Spindles ◽

Mitotic Chromosomes ◽

Mitotic Apparatus ◽

Viral Origin ◽

E2 Protein ◽

Origin Binding Protein

ABSTRACT Papillomaviral DNA replicates as extrachromosomal plasmids in squamous epithelium. Viral DNA must segregate equitably into daughter cells to persist in dividing basal/parabasal cells. We have previously reported that the viral origin binding protein E2 of human papillomavirus types 11 (HPV-11), 16, and 18 colocalized with the mitotic spindles. In this study, we show the localization of the HPV-11 E2 protein to be dynamic. It colocalized with the mitotic spindles during prophase and metaphase. At anaphase, it began to migrate to the central spindle microtubules, where it remained through telophase and cytokinesis. It was additionally observed in the midbody at cytokinesis. A peptide spanning residues 285 to 308 in the carboxyl-terminal domain of HPV-11 E2 (E2C) is necessary and sufficient to confer localization on the mitotic spindles. This region is conserved in HPV-11, -16, and -18 and bovine papillomavirus type 4 (BPV-4) E2 and is also required for the respective E2C to colocalize with the mitotic spindles. The E2 protein of bovine papillomavirus type 1 is tethered to the mitotic chromosomes via the cellular protein Brd4. However, the HPV-11 E2 protein did not associate with Brd4 during mitosis. Lastly, a chimeric BPV-1 E2C containing the spindle localization domain from HPV-11 E2C gained the ability to localize to the mitotic spindles, whereas the reciprocal chimera lost the ability. We conclude that this region of HPV E2C is critical for localization with the mitotic apparatus, enabling the HPV DNA to sustain persistent infections.

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Expression, Purification, and Antibody Binding Activity of Human Papillomavirus 16 L1 Protein Fused to Maltose Binding Protein

Protein and Peptide Letters ◽

10.2174/092986607780782722 ◽

2007 ◽

Vol 14 (5) ◽

pp. 417-424 ◽

Cited By ~ 5

Author(s):

Hee-Jeong Cho ◽

Moon Sun Hahm ◽

Myung Kuk Kim ◽

In-Kwon Han ◽

Woon-Won Jung ◽

...

Keyword(s):

Human Papillomavirus ◽

Binding Protein ◽

Maltose Binding Protein ◽

Binding Activity ◽

Antibody Binding ◽

Human Papillomavirus 16 ◽

L1 Protein

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Significance of p53-Binding Protein 1 Nuclear Foci in Cervical Squamous Intraepithelial Lesions: Association With High-Risk Human Papillomavirus Infection and P16INK4a Expression

Cancer Control ◽

10.1177/1073274819901170 ◽

2020 ◽

Vol 27 (1) ◽

pp. 107327481990117

Author(s):

Sayaka Kawashita ◽

Katsuya Matsuda ◽

Hisayoshi Kondo ◽

Yuriko Kitajima ◽

Yuri Hasegawa ◽

...

Keyword(s):

In Situ Hybridization ◽

Human Papillomavirus ◽

High Risk ◽

Binding Protein ◽

Histological Grade ◽

Neoplastic Progression ◽

Cervical Lesions ◽

Nuclear Foci ◽

The Impact

As p53-binding protein 1 (53BP1) localizes to the sites of DNA double-strand breaks and rapidly forms nuclear foci (NF), and its presence may be an indicator of endogenous genomic instability (GIN). We previously showed that 53BP1 NF in cervical cells increase with neoplastic progression, indicating the significance of 53BP1 expression for the estimation of malignant potential during cervical carcinogenesis. This study aimed to further elucidate the impact of 53BP1 expression as a biomarker for cervical squamous intraepithelial lesion (SIL). A total of 81 tissue samples, including 17 of normal cervical epithelium, 22 of cervical intraepithelial neoplasia (CIN) 1, 21 of CIN2, and 21 of CIN3, from patients positive for high-risk human papillomavirus (HR-HPV) were used for double-label immunofluorescence of 53BP1 and Ki-67/p16INK4a expression and HR-HPV in situ hybridization. We analyzed associations between 53BP1 expression type with parameters such as CIN grade, HR-HPV infection status, p16INK4a expression, and CIN prognosis. Expression type of 53BP1 was significantly associated with histological grade of CIN and HR-HPV in situ hybridization signal pattern ( P < .0001). There was a significant correlation between 53BP1 and p16INK4a expression levels ( r = .73, P < .0001). However, there was no association between 53BP1 expression type and CIN prognosis. We propose that 53BP1 expression type is a valuable biomarker for SIL, which can help estimate the grade and GIN of cervical lesions reflecting replication stress caused by the integration of HR-HPV to the host genome.

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