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Activity-Based Imaging and Biochemical Profiling Tools for Analysis of the Cancer Degradome

  • Vincent Dive
  • Margot G. Paulick
  • J. Oliver McIntyre
  • Lynn M. Matrisian
  • Matthew Bogyo

Abstract

Proteases represent one of the largest and most well-characterized families of enzymes in the human genome. Furthermore, there are many human health conditions associated with alterations in protease activity and function, most notably cancer. Frequently, associations between specific proteases and a given disease are correlative, and there is a need to determine the significance of direct causal relationships. Unfortunately, our understanding of protease function in the context of complex proteolytic cascades involved in human biology remains in its infancy. This gap in our knowledge has to do with the high degree of complexity both at the level of expression and also at the level of posttranslational regulation of proteases involved in the pathways that regulate human physiology or disease pathology. Thus, in order to begin to decipher complex regulatory networks and to assign function to the more than 500 proteases in the human genome, tools will need to be generated that allow direct assessment of protease activity in the context of complex biological systems. In this chapter, we will focus on the recent advances in the development and application of protease probes that can be used to directly monitor levels of active proteases in biological environments ranging from whole cell lysates to whole organisms. This chapter focuses on new developments in the field of small molecule activity-based probes and the development of protease sensors based on substrates. The goal of this chapter is to give the reader an update on our ability to spy on proteases at the level of their enzymatic activity.

Keywords

Cysteine Protease Resonance Energy Transfer Chem Biol Serine Hydrolase Lysosomal Cysteine Protease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science + Business Media, LLC 2008

Authors and Affiliations

  • Vincent Dive
    • 1
  • Margot G. Paulick
    • 2
  • J. Oliver McIntyre
    • 3
  • Lynn M. Matrisian
    • 3
  • Matthew Bogyo
    • 4
  1. 1.CEA, Institut de Biologie et des Technologies de SaclayService d’Ingénierie Moléculaire des ProéinesGif/Yvette CedexFrance
  2. 2.Department of Pathology and Microbiology and ImmunologyStanford UniversityStanfordUSA
  3. 3.Department of Cancer BiologyVanderbilt UniversityNashvilleUSA
  4. 4.Dept. of PathologyStanford UniversityStanford

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