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Activity-based protein profiling for biochemical pathway discovery in cancer
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Activity-based protein profiling for biochemical pathway discovery in cancer
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Journal Article
Activity-based protein profiling for biochemical pathway discovery in cancer
2010
Overview
Key Points
Activity-based protein profiling (ABPP) facilitates the discovery of deregulated enzymes in cancer.
Competitive ABPP yields selective inhibitors for functional characterization of cancer enzymes.
ABPP can be integrated with metabolomics to map deregulated enzymatic pathways in cancer.
ABPP can be integrated with other proteomic methods to map proteolytic pathways in cancer.
ABPP probes can be used to image tumour development in living animals.
This Review focuses on activity-based protein profiling, which enables the discovery of cancer-relevant enzymes and selective pharmacological probes to perturb and characterize these proteins in tumour cells. When ABPP is integrated with other large-scale profiling methods, it can provide insight into the metabolic and signalling pathways that support cancer pathogenesis and indicate new strategies for treatment.
Large-scale profiling methods have uncovered numerous gene and protein expression changes that correlate with tumorigenesis. However, determining the relevance of these expression changes and which biochemical pathways they affect has been hindered by our incomplete understanding of the proteome and its myriad functions and modes of regulation. Activity-based profiling platforms enable both the discovery of cancer-relevant enzymes and selective pharmacological probes to perturb and characterize these proteins in tumour cells. When integrated with other large-scale profiling methods, activity-based proteomics can provide insight into the metabolic and signalling pathways that support cancer pathogenesis and illuminate new strategies for disease diagnosis and treatment.
