home > faculty > Schlieker

CHRISTIAN SCHLIEKER

Defects in protein folding have been identified as underlying cause for a steadily increasing number of congenital diseases, yet the connection between protein misfolding and disease remains poorly understood.  My lab studies how a cell decides whether a misfolded protein is repaired or must be degraded, and how this process is controlled at the molecular level.

In higher eukaryotes, the ubiquitin/proteasome system and the lysosome cooperate to dispose of defective proteins.  We apply a combination of structural, biochemical and cell biological approaches to dissect the multiple roles of ubiquitin in protein quality control.  One of our immediate goals is to decipher the largely enigmatic role of deubiquitinating enzymes, which counterbalance the activity of ubiquitin ligases.  Our long-term goal is to understand why and how misfolded proteins are partitioned between cellular compartments, and to dissect how individual branches of the protein quality control network are wired to form a robust network.

Another area of interest revolves around urm1 (ubiquitin-related modifier-1), perhaps the most unusual ubiquitin-like modifier.  We have recently assigned urm1 to an unexpected role in tRNA modifications, and we continue to explore the biological function of these modifications in mammalian cells.

Selected Publications
Schlieker, C., Weihofen, W. A., Frijns, E., Kattenhorn, L. M., Gaudet, R., and Ploegh, H. L. Structure of a herpesvirus-encoded cysteine protease reveals a unique class of deubiquitinating enzymes. Mol. Cell 25, 677-687 (2007)

Schlieker, C. D., Van der Veen, A. G., Damon, J. R., Spooner, E., and Ploegh, H. L. A functional proteomics approach links the ubiquitin-related modifier Urm1 to a tRNA modification pathway. Proc. Natl. Acad. Sci. USA 105, 18255-18260 (2008)

Ernst, R., Mueller, B., Ploegh, H. L. and Schlieker, C. The otubain YOD1 is a deubiquitinating enzyme that associates with p97 to facilitate protein dislocation from the ER.  Mol. Cell, In press.

Last Updated 09-16-09