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An AIDS-related virus tricks cells to become tumors, new Penn study finds

Researchers at the University of Pennsylvania School of Medicine have discovered how the Kaposi's sarcoma-associated herpesvirus (KSHV) subverts a normal cell process in order to promote tumor growth. The finding, published in the most recent issue of PLoS Pathogens, offers new potential strategies for treating Kaposi's sarcoma and other cancers associated with viruses.

KSHV is an opportunistic pathogen that rarely affects individuals with normal immune systems. However, HIV/AIDS patients and those who are immune suppressed such as organ transplant patients are at high risk for developing Kaposi's sarcoma and another cancer called primary effusion lymphoma.

The study describes how a KSHV-encoded protein, called latency-associated nuclear antigen, or LANA, tricks the cell into destroying two major suppressors of tumor growth called von Hippel Lindau (VHL) and p53. "In addition, we have shown that when LANA expression was blocked, the tumor suppressors again become stable suggesting a direct role of the viral protein in regulation of these major cell proteins," says lead author Erle Robertson, PhD, Professor of Microbiology and the Director of Tumor Virology at Penn's Abramson Cancer Center.

Marked for Disposal The trick is played out in a cell process called ubiquitylation. This refers to a pathway in all cells whereby a protein aptly named ubiquitin binds to cellular proteins and marks them for degradation. This process can be likened to putting out the garbage for disposal.

Ubiquitylation and degradation involve a complex set of proteins in addition to ubiquitin. "We found that the viral LANA has an amino acid motif that mimics non-viral cell proteins usually involved in the ubiquitylation process," says Robertson. This motif, or stretch of amino acids, normally enables LANA to bind to tumor suppressors p53 or VHL, thus bringing them into the active ubiquitylation complex. Once in the complex, the tumor suppressors are target
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Source:University of Pennsylvania School of Medicine


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