Protease Trafficking


Research Projects Brix – Protease Trafficking

In cell-based assays, trafficking analyses were performed that comprise expression of GFP-tagged cathepsins with or without active-site-mutations, cathepsin variants derived from tumor cells, as well as the use of activity-based probes to visualize transport and proteolytic activities of the enzymes in living cells. The results proved that the primary sequence and proper folding of the proteases is sufficient to correctly target cysteine cathepsins into endocytic compartments of normal epithelial cells. However, altered trafficking in carcinoma cells may result in mislocalization of cysteine cathepsins. Hence, cellular transport logistics do not depend on the cargo but rather on the cells themselves. This notion bears implications for the molecular mechanisms underlying altered transport pathways of cysteine cathepsins in pathological conditions such as cancer.

Supported by DFG BR1308 / 6-1, 6-2 in the framework of the FOR 367; DFG BR1308 / 10-1, and 7-1, 7-2, 7-3 in the framework of the KFO 115; Deutscher Akademischer Austauschdienst (DAAD), Research Grants – Doctoral Programmes in Germany, PRNo. 91534725 to AAH


  • Al-Hashimi, A., V. Venugopalan, M. Rehders, N. Sereesongsaeng, Z. Hein, S. Springer, E. Weber, D. Führer, M.S. Bogyo, C.J. Scott, R.E. Burden, and K. Brix (2020b) Procathepsin V Is Secreted in a TSH Regulated Manner from Human Thyroid Epithelial Cells and Is Accessible to an Activity-Based Probe. Int. J. Mol. Sci. 2020, 21(23), 9140; doi:10.3390/ijms21239140
  • Al-Hashimi, A., V. Venugopalan, N. Sereesongsaeng, S. Tedelind, A.M. Pinzaru, Z. Hein, S. Springer, E. Weber, D. Führer, C.J. Scott, R.E. Burden, and K. Brix (2020a) Significance of nuclear cathepsin V in normal thyroid epithelial and carcinoma cells. BBA – Molecular Cell Research 1867, 118846. ShareLink:;
  • Brix, K. (2018). Host cell proteases: cathepsins. In: Activation of Viruses by Host Proteases, edited by Eva Böttcher-Friebertshäuser, Wolfgang Garten, and Hans Dieter Klenk. Springer-Verlag.
  • Couture, F., A.M. Jansen, P. Taghert, and K. Brix (2017). EJCB – Molecular basis of protein fates in the secretory and endocytic pathways, and beyond. Eur. J. Cell Biol. 96, 369–371. Doi:10.1016/j.ejcb.2017.06.006
  • Tamhane, T., R. Illukkumbura, S. Lu, G.M. Maelandsmo, M.H. Haugen, and K. Brix (2016). Nuclear cathepsin L activity is required for cell cycle progression of colorectal carcinoma cells. Biochimie 122, 208-218. doi: 10.1016/j.biochi.2015.09.003
  • Tamhane, T., B.K. Wolters, R. Illukkumbura, G.M. Maelandsmo, M.H. Haugen, and K. Brix (2015). Construction of a plasmid coding for green fluorescent protein tagged cathepsin L and data on expression in colorectal carcinoma cells. Data in Brief 5, 468-475. doi: 10.1016/j.dib.2015.09.022
  • Brix, K., J. McInnes, A. Al-Hashimi, M. Rehders, T. Tamhane, M.H. Haugen (2015). Proteolysis mediated by cysteine cathepsins and legumain – recent advances and cell biological challenges. Protoplasma 252, 755-774. doi: 10.1007/s00709-014-0730-0.
  • Haugen, M.H., K. Boye, J.M. Nesland, S.J. Pettersen, E.V. Egeland, T. Tamhane, K. Brix, G.M. Maelandsmo, and K. Flatmark (2015). High expression of the cysteine proteinase legumain in colorectal cancer – Implications for therapeutic targeting. Eur. J. Cancer 51, 9-17. doi: 10.1016/j.ejca.2014.10.020.
  • Haugen, M.H., H.T. Johansen, S.J. Pettersen, R. Solberg, K. Brix, K. Flatmark, and G.M. Maelandsmo (2013). Nuclear legumain activity in colorectal cancer. PLoS One 8(1), e52980. Doi: 10.1371/journal.pone.0052980
  • Brix, K., C.J. Scott, M.M.S. Heck (2013) Compartmentalization of Proteolysis. In: Proteases: Structure and Function, edited by Klaudia Brix and Walter Stöcker, Springer-Verlag Wien.
  • Tedelind, S., S. Jordans, H. Resemann, G. Blum, M. Bogyo, D. Führer, and K. Brix (2011). Cathepsin B trafficking in thyroid carcinoma cells. Thyroid Research 4 (Suppl 1), S2. doi:10.1186/1756-6614-4-S1-S2
  • Arampatzidou, M., M. Rehders, S. Dauth, D.M.T. Yu, S. Tedelind, and K. Brix (2011). Imaging of protease functions – current guide to spotting cysteine cathepsins in classical and novel scenes of action in mammalian epithelial cells and tissues. It. J. Anat. Embryol. 116, 1-19.
  • Tedelind, S., K. Poliakova, A. Valeta, R. Hunegnaw, E. Lemma Yemanaberhan, N.-E. Heldin, J. Kurebayashi, E. Weber, N. Kopitar-Jerala, B. Turk, M. Bogyo, and K. Brix (2010). Nuclear cysteine cathepsin variants in thyroid carcinoma cells. Biol. Chem. 391, 923-935.
  • Mayer, K., M.E. Iolyeva, U. Meyer-Grahle, and K. Brix (2008). Intestine-specific expression of green fluorescent protein-tagged cathepsin B: proof-of-principle experiments. Biol. Chem. 389, 1085-1096. doi 10.1515/BC.2008.360
  • Brix, K., A. Dunkhorst, K. Mayer, and S. Jordans (2008). Cysteine cathepsins: Cellular roadmap to different functions. Biochimie 90, 194-207. doi:10.1016/j.biochi.2007.07.024
  • Brix, K., and S. Jordans (2005). News & Views: Watching proteases in action. Nature Chem. Biol. 1, 186-187.
  • Brix, K. (2005). Chapter 05: Lysosomal Proteases: Revival of the Sleeping Beauty. In: Lysosomes, edited by Paul Saftig, Landes Bioscience.
  • Linke, M., V. Herzog, and K. Brix (2002). Trafficking of lysosomal cathepsin B – green fluorescent protein to the surface of thyroid epithelial cells involves the endosomal/lysosomal compartment. J. Cell Sci. 115, 4877-4889.
  • Linke, M., S. Jordans, L. Mach, V. Herzog, and K. Brix (2002). Thyroid stimulating hormone upregulates secretion of cathepsin B from thyroid epithelial cells. Biol. Chem. 383, 773-784.