scholarly journals Mutagenic Potential ofBos taurusPapillomavirus Type 1 E6 Recombinant Protein: First Description

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Rodrigo Pinheiro Araldi ◽  
Jacqueline Mazzuchelli-de-Souza ◽  
Diego Grando Modolo ◽  
Edislane Barreiros de Souza ◽  
Thatiana Corrêa de Melo ◽  
...  

Bovine papillomavirus (BPV) is considered a useful model to study HPV oncogenic process. BPV interacts with the host chromatin, resulting in DNA damage, which is attributed to E5, E6, and E7 viral oncoproteins activity. However, the oncogenic mechanisms of BPV E6 oncoproteinper seremain unknown. This study aimed to evaluate the mutagenic potential ofBos tauruspapillomavirus type 1 (BPV-1) E6 recombinant oncoprotein by the cytokinesis-block micronucleus assay (CBMNA) and comet assay (CA). Peripheral blood samples of five calves were collected. Samples were subjected to molecular diagnosis, which did not reveal presence of BPV sequences. Samples were treated with 1 μg/mL of BPV-1 E6 oncoprotein and 50 μg/mL of cyclophosphamide (positive control). Negative controls were not submitted to any treatment. The samples were submitted to the CBMNA and CA. The results showed that BPV E6 oncoprotein induces clastogenesisper se, which is indicative of genomic instability. These results allowed better understanding the mechanism of cancer promotion associated with the BPV E6 oncoprotein and revealed that this oncoprotein can induce carcinogenesisper se. E6 recombinant oncoprotein has been suggested as a possible vaccine candidate. Results pointed out that BPV E6 recombinant oncoprotein modifications are required to use it as vaccine.

Oncogene ◽  
2005 ◽  
Vol 24 (24) ◽  
pp. 3942-3953 ◽  
Author(s):  
Yun Liu ◽  
Zhiguo Liu ◽  
Hua Gao ◽  
You Zhou ◽  
Elliot J Androphy ◽  
...  

2008 ◽  
Vol 83 (1) ◽  
pp. 167-180 ◽  
Author(s):  
Rong Jia ◽  
Xuefeng Liu ◽  
Mingfang Tao ◽  
Michael Kruhlak ◽  
Ming Guo ◽  
...  

ABSTRACT The viral early-to-late switch of papillomavirus infection is tightly linked to keratinocyte differentiation and is mediated in part by alternative mRNA splicing. Here, we report that SRp20, a cellular splicing factor, controls the early-to-late switch via interactions with A/C-rich RNA elements. An A/C-rich SE4 element regulates the selection of a bovine papillomavirus type 1 (BPV-1) late-specific splice site, and binding of SRp20 to SE4 suppresses this selection. Expression of late BPV-1 L1 or human papillomavirus (HPV) L1, the major capsid protein, inversely correlates with SRp20 levels in the terminally differentiated keratinocytes. In HPV type 16, a similar SRp20-interacting element also controls the viral early-to-late switch. Keratinocytes in raft cultures, which support L1 expression, make considerably less SRp20 than keratinocytes in monolayer cultures, which do not support L1 expression. Conversely, abundant SRp20 in cancer cells or undifferentiated keratinocytes is important for the expression of the viral early E6 and E7 by promoting the expression of cellular transcription factor SP1 for transactivation of viral early promoters.


2011 ◽  
Vol 85 (20) ◽  
pp. 10487-10498 ◽  
Author(s):  
M. A. Morrison ◽  
R. J. Morreale ◽  
S. Akunuru ◽  
M. Kofron ◽  
Y. Zheng ◽  
...  

2011 ◽  
Vol 92 (11) ◽  
pp. 2608-2619 ◽  
Author(s):  
ZhengQiang Yuan ◽  
Elizabeth A. Gault ◽  
M. Saveria Campo ◽  
Lubna Nasir

Equine sarcoids represent the most common skin tumours in equids worldwide, characterized by extensive invasion and infiltration of lymphatics, rare regression and high recurrence after surgical intervention. Bovine papillomavirus type 1 (BPV-1) activity is necessary for the transformation phenotype of equine fibroblasts. Among the many changes induced by BPV-1, matrix metalloproteinase 1 (MMP-1) upregulation contributes to the invasiveness of equine fibroblasts. However, it is not yet known how BPV-1 proteins regulate equine MMP-1 expression. To elucidate this mechanism, the equine MMP-1 promoter was cloned and analysed. A putative activator protein-1 (AP-1)-binding site was demonstrated to be crucial for upregulated MMP-1 promoter activity by BPV-1. BPV-1 E6 and E7 proteins increased MMP-1 promoter activity, and inhibition of BPV-1 gene expression by small interfering RNA significantly reduced the promoter activity. c-Jun and Fra-1, two components of the AP-1 transcription factor complex, were overexpressed and activated by BPV-1 in equine fibroblasts. Finally, BPV-1 E5, E6 and E7 proteins increased MMP-1 mRNA and protein expression. In conclusion, the expression of MMP-1 can be enhanced by BPV-1 oncoproteins E6 and E7 through the AP-1 transcription factor and by E5 via an indirect mechanism. These findings shed light on the mechanism of BPV-1-mediated equine fibroblast infiltration and indicate that both BPV-1 oncoproteins and AP-1 could be potential targets for equine sarcoid therapy.


2000 ◽  
Vol 81 (11) ◽  
pp. 2617-2623 ◽  
Author(s):  
Holger Zimmermann ◽  
Choon-Heng Koh ◽  
Roland Degenkolbe ◽  
Mark J. O’Connor ◽  
Andreas Müller ◽  
...  

The E6 oncoprotein of bovine papillomavirus type 1 (BPV-1) can transform cells independently of p53 degradation. The precise mechanisms underlying this transformation are not yet completely understood. Here it is shown that BPV-1 E6 interacts with CBP/p300 in the same way as described for the E6 proteins of oncogenic human papillomaviruses. This interaction results in an inhibition of the transcriptional coactivator function of CBP/p300 required by p53 and probably by other transcription factors. The comparison of the CBP/p300-binding properties of BPV-1 E6 mutants previously characterized in transcription and transformation studies suggests (i) that the E6–CBP/p300 interaction may be necessary, but not sufficient, for cell transformation, and (ii) that the transcriptional activator function, inherent to the E6 protein, is not derived from forming a complex with CBP/p300.


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