Direct Measurement of Cathepsin B Activity in the Cytosol of Apoptotic Cells by an Activity-Based Probe

Matthew R. Pratt, Matthew D. Sekedat, Kyle P. Chiang, Tom W. Muir

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Cells control their own death through a program termed apoptosis, which is indispensable for development and homeostasis in all metazoans. Lysosomal cysteine proteases are not normally thought of as participating in apoptosis; however, recent reports have shown that the cathepsin proteases can be released from the lysosome during apoptosis, where they can participate in cell death. We report here the development of an activity-based probe that, under optimized conditions, reports on cathepsin B activity only in apoptotic cells by reading out the release of cathepsin B from the lysosomes. Biochemical characterization of apoptosis in cells from cathepsin B null mice shows delayed and suboptimal activation of caspases. Our data further supports a role for cathepsin B in the cytosol as a positive regulator of a cell death feed-forward loop and provides a chemical tool for future investigations.

Original languageEnglish (US)
Pages (from-to)1001-1012
Number of pages12
JournalChemistry and Biology
Volume16
Issue number9
DOIs
StatePublished - Sep 25 2009

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Keywords

  • CELLBIO
  • CHEMBIO
  • SIGNALING

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