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Inhibition of ubiquitin/proteasome-dependent protein degradation by the Gly-Ala repeat domain of the Epstein–Barr virus nuclear antigen 1

Overview of attention for article published in Proceedings of the National Academy of Sciences of the United States of America, November 1997
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Title
Inhibition of ubiquitin/proteasome-dependent protein degradation by the Gly-Ala repeat domain of the Epstein–Barr virus nuclear antigen 1
Published in
Proceedings of the National Academy of Sciences of the United States of America, November 1997
DOI 10.1073/pnas.94.23.12616
Pubmed ID
Authors

Jelena Levitskaya, Anatoly Sharipo, Ainars Leonchiks, Aaron Ciechanover, Maria G. Masucci

Abstract

The Epstein-Barr virus (EBV) encoded nuclear antigen (EBNA) 1 is expressed in latently infected B lymphocytes that persist for life in healthy virus carriers and is the only viral protein regularly detected in all EBV associated malignancies. The Gly-Ala repeat domain of EBNA1 was shown to inhibit in cis the presentation of major histocompatibility complex (MHC) class I restricted cytotoxic T cell epitopes from EBNA4. It appears that the majority of antigens presented via the MHC I pathway are subject to ATP-dependent ubiquitination and degradation by the proteasome. We have investigated the influence of the repeat on this process by comparing the degradation of EBNA1, EBNA4, and Gly-Ala containing EBNA4 chimeras in a cell-free system. EBNA4 was efficiently degraded in an ATP/ubiquitin/proteasome-dependent fashion whereas EBNA1 was resistant to degradation. Processing of EBNA1 was restored by deletion of the Gly-Ala domain whereas insertion of Gly-Ala repeats of various lengths and in different positions prevented the degradation of EBNA4 without appreciable effect on ubiquitination. Inhibition was also achieved by insertion of a Pro-Ala coding sequence. The results suggest that the repeat may affect MHC I restricted responses by inhibiting antigen processing via the ubiquitin/proteasome pathway. The presence of regularly interspersed Ala residues appears to be important for the effect.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 124 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 3 2%
Netherlands 3 2%
United Kingdom 2 2%
Malaysia 1 <1%
Unknown 115 93%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 27 22%
Researcher 22 18%
Student > Master 13 10%
Student > Bachelor 9 7%
Professor > Associate Professor 6 5%
Other 18 15%
Unknown 29 23%
Readers by discipline Count As %
Agricultural and Biological Sciences 35 28%
Biochemistry, Genetics and Molecular Biology 24 19%
Medicine and Dentistry 12 10%
Immunology and Microbiology 11 9%
Pharmacology, Toxicology and Pharmaceutical Science 2 2%
Other 9 7%
Unknown 31 25%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 16 March 2021.
All research outputs
#8,219,054
of 24,622,191 outputs
Outputs from Proceedings of the National Academy of Sciences of the United States of America
#64,491
of 101,438 outputs
Outputs of similar age
#10,082
of 32,596 outputs
Outputs of similar age from Proceedings of the National Academy of Sciences of the United States of America
#278
of 524 outputs
Altmetric has tracked 24,622,191 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 101,438 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 38.8. This one is in the 15th percentile – i.e., 15% 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 32,596 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 9th percentile – i.e., 9% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 524 others from the same source and published within six weeks on either side of this one. This one is in the 4th percentile – i.e., 4% of its contemporaries scored the same or lower than it.