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Study offers innovative profile of enzyme that aids tumor growth

"Using a combination of enzyme activity and metabolite profiling, we determined that this protein-whose function was previously unknown-serves as a key regulator of a lipid signaling network that contributes to cancer," said Benjamin F. Cravatt, a Scripps Research professor and a member of its Skaggs Institute for Chemical Biology who led the study. "The heightened expression of KIAA1363 in several cancers indicates that it may be a critical factor in tumorgenesis. In addition, network components, including KIAA1363 itself, might be considered potential diagnostic markers for ovarian cancer."

This experimental method of integrated molecular profiling used in the study should also advance the functional study of metabolic enzymes in any biological system, according to Cravatt.

To date, understanding the roles of uncharacterized enzymes in cell physiology and pathology has remained problematic. Typically, the activities of enzymes have been studied in vitro using purified protein preparations. The outcome of these test-tube studies can be difficult to translate into clear characterizations of the roles that enzymes play in living systems, where these proteins generally operate within larger metabolic networks.

A primary advantage of metabolite profiling in natural biological systems is that it circumvents some of the most time-consuming steps that accompany in vitro enzyme analysis while generating data more directly related to their naturally occurring activities.

"Our hypothesis was that the determination of catalytic activities for enzymes like KIAA1363 could be done directly in living systems through the integrated application of profiling technologies that survey both the enzymatic proteome and its primary biochemical output, the metabolome," Cravatt said.

So, the team drew both on proteomics-the large-scale study of the structure and function of proteins-and metabolomics-the systematic study of cellular processes,
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Source:Scripps Research Institute


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