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An AIDS-related virus reveals more ways to cause cancer, Penn researchers find
Date:10/8/2007

PHILADELPHIA Researchers at the University of Pennsylvania School of Medicine have shed new light on how Kaposis Sarcoma-associated Herpes Virus (KSHV) subverts normal cell machinery to cause cancer. A KSHV protein called latency-associated nuclear antigen, LANA for short, helps the virus hide out from the immune system in infected cells. When LANA takes the place of other proteins that control cell growth, it can cause uncontrolled cell replication.

The findings appear in a recent issue of the Proceedings of the National Academy of Sciences.

This is the first report of LANA interfering with the crucial cellular protein called intracellular Notch, says lead author Erle Robertson, PhD, Professor of Microbiology and the Program Leader of Tumor Virology at Penns Abramson Cancer Center. Notch is a signaling molecule that triggers cell development and maintains the stability of cells in many organs, such as the brain, heart, blood, and muscle.

Intracellular notch, or ICN, promotes cell growth and proliferation, therefore it must be regulated so that these processes do not lead to cancer, says Robertson. We found that regulation of ICN through binding to another protein called Sel10, a cell-cycle regulatory protein, is derailed. The large complex of ICN, Sel10, and other factors is marked for degradation by a process called ubiquitination, says Robertson. In normal uninfected cells, the level of ICN, and thus cell growth and proliferation, is fine-tuned by regulating ICN degradation.

LANA interferes with the degradation of ICN because it competes with ICN for the same binding site on Sel10. If LANA sits on Sel10, ICN cannot be degraded and cell growth and proliferation are no longer controlled. Kaposis sarcoma and primary effusion lymphoma are two of the viral-associated cancers that are common in immune-compromised patients.

This is the second mechanism discovered by Robertson and his associates by whi
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert

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