Birgitta Tomkinson research group

Structure, function and physiological role of tripeptidyl-peptidase II

Intracellular protein degradation is as important for regulating the concentration of specific proteins in the cell as protein synthesis, but much less well characterized. Protein degradation is malfunctioning in a number of diseases such as cancer, muscle wasting and Alzheimers disease. Tripeptidyl-peptidase II (TPP II) is an important player in intracellular proteolysis, and the ultimate goal of our work is to determine the specific physiological role of the enzyme in this process. TPP II is a huge enzyme complex with a widespread distribution in eukaryotic cells and the ability to cleave oligopeptides into tripeptides. Our main focus is a biochemical characterization of TPP II, in order to investigate how its substrate specificity is determined and how oligomerization is regulated. We are also investigating how expression of this enzyme is regulated. This type of investigations will provide a basis for construction of e.g. specific inhibitors of TPP II. Since TPP II appears to be important for inactivation of the neuropeptide cholecystokinin and also for tumour progression, it is a potential drug target