( Although new HIV treatments have drasti...)How an AIDS-Related Cancer Unleashes Inflammation

Don Ganem, a Howard Hughes Medical Institute (HHMI) investigator, and HHMI associate Craig McCormick, who are both at the University of California, San Francisco, published their findings in the February 4, 2005, issue of the journal Science.

Ganem and McCormick dedicated the Science article to the memory of Robert Sadler, a former HHMI associate in Ganem's lab who discovered kaposin B. Sadler was killed in 1999 by stray bullets fired into a San Francisco nightclub.

According to Ganem, early studies of Kaposi's sarcoma (KS) indicated that the abnormal growth of infected cells required the overproduction of cytokines ?immune system proteins that trigger the cell's inflammatory response. A central question, he said, has been how does the Kaposi's sarcoma-associated herpesvirus that causes KS initiate cytokine production?

"While there are many genes in the viral genome that are capable of inducing cytokine production, the mechanism underlying this induction has remained unknown," said Ganem.

In their studies, McCormick and Ganem concentrated on one protein called kaposin B, which was discovered in Ganem's laboratory, but whose function remained unknown. "The sequence of the kaposin B gene is very unusual; there's no homology to any known gene," said Ganem. "So, we had no clue as to what the protein did. Since it was a very simple protein, we believed that it had no enzymatic function itself, but acted by binding to or activating other proteins," he said.

Thus, the researchers conducted experiments in which they isolated proteins that bound with kaposin B in the cell. That screening revealed that kaposin
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Source:Howard Hughes Medical Institute