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The Beginning and End of Proteins

14 June 2010 Albert-Ludwigs-Universität Freiburg

Cells and tissues include thousands of different proteins – the so-called proteome. These proteins are subject to constant change. Parts of proteins can be removed, for instance, leading to shortened protein variants with new functions. The „cutting up“ of proteins is referred to as proteolysis and plays an important role in the processes of diseases such as cancer. Scientists usually do not know which proteins have been cut up, and this knowledge gap has severely hampered the development of certain medicines.

The cutting up of a protein leads to clippings which are identified by their new protein ends. Proteins have two chemically distinct ends: the amino-terminus and the carboxy-terminus. Scientists have been able to identify new amino-termini in cells and tissues created by proteolysis for some time now, providing fascinating insight into the proteolytic cutting processes. However, they have not yet succeeded in analyzing carboxy-termini in this way. Our understanding of cellular proteolysis has thus remained incomplete.

A German-Canadian research team including Dr. Oliver Schilling from the Institute of Molecular Medicine and Cell Research of the University of Freiburg as well as scientists from the University of British Columbia has now developed a method for analyzing protein carboxy-termini in cells and tissues. The team’s findings have now been published in the journal „Nature Methods“. The researchers identified carboxy-terminal sequences through mass spectrometry in a multi-stage procedure. Initial findings reveal an unexpectedly high degree of cellular proteolysis: Approximately 40 percent of the identified carboxy-termini are the result of a molecular cleavage. Scientists at the Institute of Molecular Medicine and Cell Research are now using the method to understand how so-called cathepsin proteases influence the development of cancer.

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