Protease Found that Regulates HOX Gene Expression

Researchers have found a novel protease, Taspase1, which cuts the large protein encoded by the mixed linkage leukemia (MLL) gene into two active fragments that regulate HOX gene expression. When a mutation disrupts the protease, MLL accumulates and the loss of proper HOX expression causes a rare type of juvenile leukemia.

Investigators at Harvard Medical School (Boston, MA, USA; www.harvard.edu) reported in the October 31, 2003, issue of Cell that they had purified and cloned the protease responsible for cleaving the MLL protein. They called it Taspase1, because it initiates a class of endopeptidases that utilize an N-terminal threonine as the active site nucleophile to proteolyze polypeptide substrates following aspartate.

"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,” explained senior author Dr. Stanley Korsmeyer, professor of pathology at Harvard Medical School. "We would be very interested in making an inhibitor to Taspase1, which could knock the HOX genes out of action, and test whether cancers are addicted to their HOX genes.”



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