Peter Kaiser
Ph.D. University of Innsbruck (Austria), 1994
Department of Biological Chemistry
University of California, Irvine
Irvine, CA 92697
(949) 824-9442
pkaiser@uci.edu
Research Interests:
Cell cycle control; regulation of proteins by ubiquitination.
Before a normal cell develops into a tumor cell, many changes in cellular regulatory systems occur. One of the earliest events are mutations that affect cell cycle regulation. These mutations in oncogenes and tumor-suppresser genes lead to the uncontrolled cell proliferation that is characteristic for tumor cells.Understanding how the cell cycle is regulated and how uncontrolled proliferation is prevented in normal cells is the focus of my research.
Recently, the important role of ubiquitin-mediated proteolysis in the control of the cell cycle has been recognized by many laboratories. Progression through the cell cycle is prevented by cell cycle inhibitors. These inhibitors are degraded by the highly regulated ubiquitin/proteasome pathway if it is appropriate for a cell to continue the cell cycle. Proteins chosen for degradation are tagged by covalent attachment of the small ubiquitin protein (ubiqutination). Ubiquitinated proteins are then targeted for degradation by the 26S proteasome. How a cell decides when and what proteins to ubiquitinate and subsequently degrade are some of the questions my laboratory is addressing. Recently we discovered a novel (degradation-independent) role for the ubiquitin-conjugating system in the regulation of cell proliferation. Here ubiquitination directly regulates the activity but not the stability of a transcription factor. My laboratory is interested in the identification of other cell cycle regulators that are subject to this novel ubiquitin-mediated regulation and in the biochemical analysis of this novel ubiquitination process.
The budding yeast S. cerevisiae has long been used as the preferred model organism to understand both cell cycle control and regulation of the ubiquitin/proteasome pathway. My laboratory exploits the genetic, genomic and proteomic tools available in budding yeast for gene discovery and functional analysis of cell cycle regulation and ubiquitination. What we have learned from studying these processes in yeast will then be applied to analyze cell cycle regulation and ubiquitination in mammalian cells.
Selected Publications:
Karin Flick, Shahri Raasi, Hongwei Zhang, James Yen and Peter Kaiser. (2006). A Ubiquitin Interacting Motif Protects Polyubiquitinated Met4 from Degradation by the 26S Proteasome. Nature Cell Biology, 8, 509-515.
Tagwerker C., Flick K., Cui M., Guerrero C., Dou Y., Auer B., Baldi P., Huang L. and Kaiser P.. (2006). A tandem-affinity tag for two-step purification under fully denaturing conditions: Application in ubiquitin profiling and protein complex identification combined with in vivo cross-linking. Mol. Cell. Proteomics. PMID: 16432255
Guerrero C., Tagwerker C.,Kaiser P. and Huang L.. (2005). An integrated mass spectrometry-based proteomics approach -QTAX to decipher the 26S proteasome interacting network. Mol. Cell. Proteomics. PMID: 16284124
Peter Kaiser and Lan Huang (2005). Global approaches to understanding ubiquitination. Genome Biology 6, 233.
Peter Kaiser and Christian Tagwerker. (2005). Is this protein ubiquitinated?, Methods Enzymol 399C: 266-277.
Peter Kaiser and James Wohlschlegel. (2005). Identification of ubiquitination sites and determination of ubiquitin-chain architectures by mass spec, Methods Enzymol 399C: 243-248.
Su N., Flick K. and Kaiser P. (2005). The F-box protein Met30 is required for multiple steps in the budding yeast cell cycle. Mol. Cell. Biol. 25, 3875-3885.
Yen, JL., Su, N. and Kaiser P. (2005). The yeast ubiquitin ligase SCFMet30 regulates heavy metal response. Mol. Biol. Cell. 6, 1872-1882.
Flick K., Ouni I., Wohlschlegel J. A., Capati C., McDonald W. H., Yates J. R. and Kaiser P.. (2004). Proteolysis-independent Regulation of the Transcription Factor Met4 by a single K48-Linked Ubiquitin Chain. Nature Cell Biology. 6, 634-641.
Morris M., Kaiser P., Rudyak S., Baskerville C., Watson MH.and Reed S. I.. (2003). Cks1-dependent proteasome recruitment and activation of CDC20 transcription in budding yeast. Nature. 423, 1009-1013.
Strohmaier H., Spruck C. H., Kaiser P., Won K., Sangfelt O. and Reed S. I. (2001). The Human F-Box Protein, hCdc4, Targets Cyclin E for Proteolysis and is Mutated in a Breast Cancer Cell Line. Nature. 413, 316-322
Kaiser P., Flick K., Wittenberg C. and Reed S. I.. (2000). Regulation of Transcription by Ubiquitination without Proteolysis: Cdc34/SCFMet30-Mediated Inactivation of the Transcription Factor Met4. Cell 102 (3), 303-314.
Xu S., Huang H-K., Kaiser P., Latterich M. and Hunter T.. (2000). Phosphorylation and spindle pole body localization of the Cdc15p mitotic regulatory protein kinase in Saccharomyces cerevisiae.
Current Biology 10, 329-332.
Kaiser P., Moncollin V., Clarke D. J., Watson M. H., Bertolaet B. L., Reed S. I., and Bailly E. (1999). Cyclin-dependent kinase and Cks/Suc1 interact with the proteasome in yeast to control proteolysis of M-phase targets. Genes and Dev. 13, 1190-202.
Kaiser P., Sia R. A. L., Bardes E. G. S., Lew D. J., and Reed S. I. (1998). Cdc34 and the F-box protein Met30 are required for degradation of the Cdk-inhibitory kinase Swe1. Genes and Dev. 12, 2587-97.
