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Production of functional, stable, unmutated recombinant human papillomavirus E6 oncoprotein: implications for HPV-tumor diagnosis and therapy

Overview of attention for article published in Journal of Translational Medicine, July 2016
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2 tweeters

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45 Mendeley
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Title
Production of functional, stable, unmutated recombinant human papillomavirus E6 oncoprotein: implications for HPV-tumor diagnosis and therapy
Published in
Journal of Translational Medicine, July 2016
DOI 10.1186/s12967-016-0978-6
Pubmed ID
Authors

Elena Illiano, Olivia Costantina Demurtas, Silvia Massa, Paola Di Bonito, Valerio Consalvi, Roberta Chiaraluce, Carlo Zanotto, Carlo De Giuli Morghen, Antonia Radaelli, Aldo Venuti, Rosella Franconi

Abstract

High-risk human papillomaviruses (HR-HPVs) types 16 and 18 are the main etiological agents of cervical cancer, with more than 550,000 new cases each year worldwide. HPVs are also associated with other ano-genital and head-and-neck tumors. The HR-HPV E6 and E7 oncoproteins are responsible for onset and maintenance of the cell transformation state, and they represent appropriate targets for development of diagnostic and therapeutic tools. The unmutated E6 gene from HPV16 and HPV18 and from low-risk HPV11 was cloned in a prokaryotic expression vector for expression of the Histidine-tagged E6 protein (His6-E6), according to a novel procedure. The structural properties were determined using circular dichroism and fluorescence spectroscopy. His6-E6 oncoprotein immunogenicity was assessed in a mouse model, and its functionality was determined using in vitro GST pull-down and protein degradation assays. The His6-tagged E6 proteins from HPV16, HPV18, and HPV11 E6 genes, without any further modification in the amino-acid sequence, were produced in bacteria as soluble and stable molecules. Structural analyses of HPV16 His6-E6 suggests that it maintains correct folding and conformational properties. C57BL/6 mice immunized with HPV16 His6-E6 developed significant humoral immune responses. The E6 proteins from HPV16, HPV18, and HPV11 were purified according to a new procedure, and investigated for protein-protein interactions. HR-HPV His6-E6 bound p53, the PDZ1 motif from MAGI-1 proteins, the human discs large tumor suppressor, and the human ubiquitin ligase E6-associated protein, thus suggesting that it is biologically active. The purified HR-HPV E6 proteins also targeted the MAGI-3 and p53 proteins for degradation. This new procedure generates a stable, unmutated HPV16 E6 protein, which maintains the E6 properties in in vitro binding assays. This will be useful for basic studies, and for development of diagnostic kits and immunotherapies in preclinical mouse models of HPV-related tumorigenesis.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 45 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 45 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 9 20%
Researcher 7 16%
Student > Ph. D. Student 6 13%
Student > Master 6 13%
Student > Doctoral Student 2 4%
Other 4 9%
Unknown 11 24%
Readers by discipline Count As %
Medicine and Dentistry 12 27%
Biochemistry, Genetics and Molecular Biology 7 16%
Agricultural and Biological Sciences 6 13%
Pharmacology, Toxicology and Pharmaceutical Science 2 4%
Immunology and Microbiology 2 4%
Other 1 2%
Unknown 15 33%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 October 2017.
All research outputs
#7,221,608
of 12,022,940 outputs
Outputs from Journal of Translational Medicine
#1,246
of 2,331 outputs
Outputs of similar age
#136,217
of 266,550 outputs
Outputs of similar age from Journal of Translational Medicine
#43
of 88 outputs
Altmetric has tracked 12,022,940 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,331 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.3. This one is in the 37th percentile – i.e., 37% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 266,550 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 44th percentile – i.e., 44% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 88 others from the same source and published within six weeks on either side of this one. This one is in the 36th percentile – i.e., 36% of its contemporaries scored the same or lower than it.