Research Profile
Protein quality control systems ensure that all proteins are biologically active, localised to the proper cellular compartment and present in appropriate quantity. This functional state must be maintained under normal as well as under stress conditions. The failure of quality control can influence cell growth and can cause severe diseases that are based on protein folding, localisation and degradation problems. We are interested in one human member of the HtrA family of conserved serine proteases. Recent evidence suggests that HtrA1 is implicated in cancer and Alzheimer's disease and that its gene is regulated, at least in part, by epigenetic mechanisms. We will investigate how epigenetics influences HtrA1 expression in human cells.

Selected Publications
Campioni, M., Severino, A., Manente, L., Tuduce, I. L., Toldo, S., Caraglia, M., Crispi, S., Ehrmann, M., De Falco, M., De Luca, A., He, X., Maguire, J., Shridhar, V. and A. Baldi 2010. The serine protease HtrA1 specifically intercats and degrades the Tuberous Sclerosis Complex 2 protein. Mol Cancer Res., Jul 29. [Epub ahead of print]

Merdanovic, M., Mamant, N., Meltzer, M., Poepsel, S., Auckenthaler, A., Melgaard, R., Hauske, P., Nagel-Steger, L., Clarke, A. R., Kaiser, M., Huber, R., and M. Ehrmann. 2010. Determinants of structural and functional plasticity of a widely conserved protease chaperone complex. Nat. Struct. Mol. Biol., 17:837-43

Krojer, T., Sawa, J., Schäfer, E., Saibil, H. R., Ehrmann, M. and T. Clausen. 2008 Structural basis for the regulated protease and chaperone function of DegP. Nature 453:885-890 (Article) Highlighted in 2008 Structure 16:989-990

Launay, S., Maubert, E., Lebeurrier, N., Tennstaedt, A., Campioni, M., Docagne, F., Gabriel, C., Ehrmann, M., Baldi, A., and D. Vivien 2008 HtrA1-dependent proteolysis of TGF- controls both neuronal maturation and developmental survival. Cell Death Diff., 15:1408-1416.

Grau, S., Richards, P., Kerr, B., Hughes, C., Caterson, B., Williams, A. S., Junker, U., Jones, S. A., Clausen, T. and M. Ehrmann. 2006. The role of human HtrA1 in arthritic disease. J. Biol. Chem. 281:6124-6129

Chien, J., Aletti, G., Baldi, A., Catalano, V., Muretto, P., Keeney, G.L., Kalli, K.R., Staub, J., Ehrmann, M., Cliby, W.A., Lee, Y.K., Bible, K.C., Hartmann, L.C., Kaufmann, S.H. and V. Shridhar 2006 Serine protease HtrA1 modulates chemotherapy-induced cytotoxicity. J. Clin. Invest. 116: 1994-2004

Ehrmann, M and T. Clausen. 2004 Proteolysis as a regulatory mechanism. Annu. Rev. Genet. 38: 709-724

Clausen, T, Southan, C. and Ehrmann, M 2002. The HtrA family of proteases, implications for protein composition and cell fate. Mol. Cell 10:443-455