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Genome Biol. 2008 Apr 3;9(4):R64. doi: 10.1186/gb-2008-9-4-r64.

A pathway sensor for genome-wide screens of intracellular proteolytic cleavage.

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  • 1Center for Computational and Integrative Biology, Massachusetts General Hospital, Cambridge Street, Boston, MA 02114, USA.


Protein cleavage is a central event in many regulated biological processes. We describe a system for detecting intracellular proteolysis based on non-conventional secretion of Gaussia luciferase (GLUC). GLUC exits the cell without benefit of a secretory leader peptide, but can be anchored in the cell by fusion to beta-actin. By including protease cleavage sites between GLUC and beta-actin, proteolytic cleavage can be detected. Using this assay, we have identified regulators of autophagy, apoptosis and beta-actin cleavage.

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