Related Experiment Video
Updated: Jun 23, 2026
09:14
Isolation and Quantification of Epstein-Barr Virus from the P3HR1 Cell Line
Published on: September 28, 2022
Phosphorylation sites of Epstein-Barr virus EBNA1 regulate its function.
Sarah J Duellman1, Katie L Thompson, Joshua J Coon
1McArdle Laboratory for Cancer Research, 1400 University Ave., University of Wisconsin-Madison, Madison, WI 53706, USA.
The Journal of General Virology
|May 15, 2009
Summary
Phosphorylation significantly impacts Epstein-Barr virus nuclear antigen 1 (EBNA1) functions. A mutant lacking ten phosphorylation sites showed reduced transcriptional activity and viral plasmid maintenance, crucial for EBV-related cancers.
Area of Science:
- Virology
- Molecular Biology
- Cancer Research
Background:
- Epstein-Barr virus (EBV) causes infectious mononucleosis and is linked to lymphomas and carcinomas.
- EBV nuclear antigen 1 (EBNA1) is essential in all EBV-associated malignancies, regulating viral and cellular functions.
- Understanding EBNA1 regulation is critical for targeting EBV-driven diseases.
Purpose of the Study:
- To investigate the role of phosphorylation in regulating EBNA1 functions.
- To identify specific phosphorylation sites on EBNA1 and assess their impact on its activity.
Main Methods:
- Electron-transfer dissociation tandem mass spectrometry was employed to identify phosphorylated EBNA1 residues.
- A phosphorylation-deficient mutant of EBNA1 was created by mutating ten identified phosphosites.
Main Results:
- Ten specific phosphorylated EBNA1 residues were identified.
- The phosphorylation-deficient EBNA1 mutant maintained wild-type half-life and nuclear translocation.
- This mutant exhibited significantly impaired transcriptional activation and EBV plasmid maintenance capabilities.
Conclusions:
- Phosphorylation is a key regulatory mechanism for EBNA1 function.
- Targeting EBNA1 phosphorylation may offer a strategy to inhibit EBV-driven cellular transformation and malignancy.
Related Concept Videos
01:02Phosphorylation
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
01:02Phosphorylation
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
02:54Protein Kinases and Phosphatases
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
02:54Protein Kinases and Phosphatases
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
01:20The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
01:22Amplifying Signals via Enzymatic Cascade
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...