Enzyme responsible for protein’s ‘Jekyll-and-Hyde’ personality

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Scientists identify novel enzyme with key role in leukemia protein’s normal function

Normally, a protein regulates when and how body parts develop, but when mutated, it triggers a rare, often-lethal infant leukemia called mixed lineage leukemia. The newly identified protease enzyme, Taspase1, plays a key role in the MLL protein’s dual-personality. (A protease enzyme cuts protein molecules into smaller pieces). Blocking Taspase1, Dana-Farber Cancer Institute researchers say, might provide a novel way to shut down runaway production of cancer cells. The findings were reported in the Oct. 31, 2003 issue of Cell. “These findings demonstrate that a simple protease enzyme is required for the effects of this gene (MLL) and suggests that protease inhibitors, which have been effective with relatively few side effects in other diseases, could be a reasonable way to treat cancer,” says Stanley Korsmeyer, senior author of the paper. Korsmeyer is the Sidney Farber Professor of Pathology at Harvard Medical School and a Howard Hughes Medical Institute investigator. Mixed lineage leukemia strikes fewer than 100 babies every year in the United States, but it is typically fatal in 60 percent. The research was supported in part by grants from the National Institutes of Health.