International Protease Network

Program on Apoptosis and Cell Death Research
The Burnham Institute of Medical Research
10901 N. Torrey Pines Road, San Diego, CA 92037, USA
Email: gsalvesen@burnham.org
Tel: +1-858-646-3114
Fax: +1-858-646-3172
Homepage: http://www.burnham.org/labs/Salvesen/

Research

Our research seeks to delineate the structure->activity->function algorithm as it applies to proteases and their inhibitors. Our laboratory has very broad interests in principles of proteolysis in humans, and we take multi-pronged approaches to research on proteases and their inhibitors. Apoptosis - In one approach we apply basic biochemical knowledge to investigate newly emerging principles of proteolysis in apoptotic cell death. Cell Signaling - Our laboratory is currently involved in projects to define the mechanisms that specific proteases use to regulate the SUMOylation/deSUMOylation cycle. Technology Development - We are developing proteomics based methodologies, including selective protein labeling, multi-dimensional electrophoresis, and mass spectrometry techniques, to identify the products of proteolysis in vivo.

Collaborations

Matt Bogyo, Stanford, USA
Jon Ellman, Berkeley, USA
Doug Green, Memphis, USA
John Reed, La Jolla, USA
Stefan Riedl, La Jolla, USA
Carol Troy, New York, USA
Boris Turk, Ljubljana, Slovenia
Keith Wilkinson, Atlanta, USA

Publications

Pop, C., Timmer, J., Sperandio, S. & Salvesen, G.S. (2006). The apoptosome activates caspase-9 by dimerization. Mol. Cell 22, 269-275.
Denault, J-B., Békés, M., Scott, F.L., Sexton, K.M.B., Bogyo, M. & Salvesen, G.S. (2006). Engineered hybrid dimers: Tracking the activation pathway of Caspase-7. Mol. Cell 23, 523-533.
Pop, C., Fitzgerald, P., Green, D.R. & Salvesen, G.S. (2007). Role of proteolysis in caspase-8 activation and stabilization. Biochemistry 46, 4398-4407.
Mikolajczyk, J., Drag, M., Bekes, M., Cao, J.T., Ronai, Z. & Salvesen, G.S. (2007). Small Ubiquitin-related Modifier (SUMO)-specific Proteases: Profiling The Specificities And Activities Of Human Senps.. J. Biol. Chem. 282, 26217-26224.
Timmer, J.C., Enoksson, M., Wildfang, E., Zhu, W., Igarashi, Y., Denault, J.B., Dummitt, B., Chang, Y.H., Mast, A.E., Eroshkin, A., Smith, J., Tao, W.A. & Salvesen, G.S. (2007). Profiling constitutive proteolytic events in vivo. Biochem. J. 407, 41-48.
Denault, J. B., Drag, M., Salvesen, G. S., Alves, J., Heidt, A. B., Deveraux, Q. and Harris, J. L. (2007) Small molecules not direct activators of caspases. Nat Chem Biol 3, 519.
Drag, M., Mikolajczyk, J., Krishnakumar, I.M., Huang, Z. & Salvesen, G.S. (2008) Activity profiling of human desSUMOylating enzmes (SENPs) with synthetic substrates suggests an enexpected specificity of two newly characterized members of the family. Biochem. J. 409(2):461-9.
Eckelman, B.P., Drag, M., Snipas, S.J. & Salvesen, G.S. (2008) The mechanism of peptide-binding specificity of IAP BIR domains. Cell Death Differ. 15(5):920-8.
Scott, F.L., Fuchs, G.J., Boyd, S.E., Denault, J.B., Hawkins, C.J., Dequiedt, F. & Salvesen, G.S. (2008) Caspase-8 cleaves histone deacetylase 7 and abolishes its transcription repressor function. J. Biol. Chem. 283(28):19499-510.
Scott, F. L., Stec, B., Pop, C., Dobaczewska, M. K., Lee, J. J., Monosov, E., Robinson, H., Salvesen, G. S., Schwarzenbacher, R. and Riedl, S. J. (2009) The Fas-FADD death domain complex structure unravels signalling by receptor clustering. Nature 457, 1019-1022