Proteomic Identification of Cysteine Cathepsin Substrates Shed from the Surface of Cancer Cells.

Autor:	Sobotič B; From the ‡Department of Biochemistry, Molecular and Structural Biology, Jozef Stefan Institute, Jamova cesta 39, SI-1000 Ljubljana, Slovenia; §International Postgraduate School Jozef Stefan, Jamova 39, SI-1000 Ljubljana, Slovenia;, Vizovišek M; From the ‡Department of Biochemistry, Molecular and Structural Biology, Jozef Stefan Institute, Jamova cesta 39, SI-1000 Ljubljana, Slovenia; §International Postgraduate School Jozef Stefan, Jamova 39, SI-1000 Ljubljana, Slovenia;, Vidmar R; From the ‡Department of Biochemistry, Molecular and Structural Biology, Jozef Stefan Institute, Jamova cesta 39, SI-1000 Ljubljana, Slovenia; §International Postgraduate School Jozef Stefan, Jamova 39, SI-1000 Ljubljana, Slovenia;, Van Damme P; ¶Department of Biochemistry, Ghent University, B-9000 Ghent, Belgium; ‖Department of Medical Protein Research, VIB, B-9000 Ghent, Belgium;, Gocheva V; *Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065;, Joyce JA; *Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065;, Gevaert K; ¶Department of Biochemistry, Ghent University, B-9000 Ghent, Belgium; ‖Department of Medical Protein Research, VIB, B-9000 Ghent, Belgium;, Turk V; From the ‡Department of Biochemistry, Molecular and Structural Biology, Jozef Stefan Institute, Jamova cesta 39, SI-1000 Ljubljana, Slovenia; §International Postgraduate School Jozef Stefan, Jamova 39, SI-1000 Ljubljana, Slovenia; ‡‡Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins, Jamova cesta 39, SI-1000 Ljubljana, Slovenia;, Turk B; From the ‡Department of Biochemistry, Molecular and Structural Biology, Jozef Stefan Institute, Jamova cesta 39, SI-1000 Ljubljana, Slovenia; ‡‡Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins, Jamova cesta 39, SI-1000 Ljubljana, Slovenia; §§Center of Excellence NIN, Ljubljana, Slovenia; ¶¶Faculty of Chemistry and Chemical Technology, University of Ljubljana, Slovenia., Fonović M; From the ‡Department of Biochemistry, Molecular and Structural Biology, Jozef Stefan Institute, Jamova cesta 39, SI-1000 Ljubljana, Slovenia; ‡‡Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins, Jamova cesta 39, SI-1000 Ljubljana, Slovenia; marko.fonovic@ijs.si.
Jazyk:	angličtina
Zdroj:	Molecular & cellular proteomics : MCP [Mol Cell Proteomics] 2015 Aug; Vol. 14 (8), pp. 2213-28. Date of Electronic Publication: 2015 Jun 16.
DOI:	10.1074/mcp.M114.044628
Abstrakt:	Extracellular cysteine cathepsins are known to drive cancer progression, but besides degradation of extracellular matrix proteins little is known about their physiological substrates and thus the molecular mechanisms they deploy. One of the major mechanisms used by other extracellular proteases to facilitate cancer progression is proteolytic release of the extracellular domains of transmembrane proteins or ectodomain shedding. Here we show using a mass spectrometry-based approach that cathepsins L and S act as sheddases and cleave extracellular domains of CAM adhesion proteins and transmembrane receptors from the surface of cancer cells. In cathepsin S-deficient mouse pancreatic cancers, processing of these cathepsin substrates is highly reduced, pointing to an essential role of cathepsins in extracellular shedding. In addition to influencing cell migration and invasion, shedding of surface proteins by extracellular cathepsins impacts intracellular signaling as demonstrated for regulation of Ras GTPase activity, thereby providing a putative mechanistic link between extracellular cathepsin activity and cancer progression. The MS data is available via ProteomeXchange with identifier PXD002192. (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)
Databáze:	MEDLINE
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