Title |
Inhibition of ubiquitin/proteasome-dependent protein degradation by the Gly-Ala repeat domain of the Epstein–Barr virus nuclear antigen 1
|
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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. |
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Geographical breakdown
Country | Count | As % |
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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% |