Erle S. Robertson, PhD, an Associate Professor of Microbiology who leads the Tumor Virology Program at Penn's Abramson Cancer Center, and MD/PhD student Jason Knight, published their results last week in the Proceedings of the National Academy of Sciences.
The retinoblastoma protein (Rb) is a major regulator of several genes in charge of cell proliferation and cell-cycle regulation. In the nucleus, Rb normally binds to E2F, turning off genes involved with cell proliferation. Using human cell cultures infected with the Epstein-Barr virus, the investigators found that EBNA3C recruits a group of molecules called the SCF complex, which attaches ubiquitin to Rb. This inadvertently tags Rb for degradation by the proteosome machinery, the cell's recycling plant. With Rb out of the way, the cell now reproduces uncontrollably.
"It's as simple as that, but it's a major mystery solved that many researchers have been working on for at least 15 years," says Robertson.
EBV, a member of the herpesvirus family and one of the most common human viruses, plays a role in cancers such as lymphoproliferative diseases in transplant or AIDS patients, Burkitt's lymphoma, Hodgkin's lymphoma, and nasopharyngeal carcinoma, and also causes the well-known disease infectious mononucleosis. As many as 95 percent of adults 20 years and older have been infected with EBV, but show
Source:University of Pennsylvania School of Medicine