Heparan sulfate - a master regulator of matrix metalloproteinase biology?
Final Report Abstract
The results obtained in this project confirm for the first time a global regulatory effect of HS on extracellular proteolysis. Especially the observed HS-dependent regulation of substrate cleavagesite accessibility is applicable to virtually every biological system including embryonic development as well as pathological situations like cancer progression and provide a potential explanation to differently regulated cleavage reactions in different physiological contexts. Especially the latter is of great interest for biomedical research, since the change in the metastatic potential of cancer tissue is closely related to upregulation of proteolytic activity and restructuring of the extracellular matrix, which is one of the first steps during the epithelial to mesenchymal transition leading to metastasis. A direct link between matrix remodeling through extracellular proteases as well as the glycosidase heparanase is therefore highly likely, but it is yet unclear if one process precedes and regulates the other or if both act in parallel during cancer progression.
Publications
-
(2019). Post-Translational Modification-Dependent Activity of Matrix Metalloproteinases. International Journal of Molecular Sciences. 20(12), 3077
Madzharova, E., Kastl, P., Sabino, F., & auf dem Keller, U.
-
(2020). Combinatorial degradomics: Precision tools to unveil proteolytic processes in biological systems. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 1868(6), 140392
Savickas, S., Kastl, P., & auf dem Keller, U.
