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Between the 1950s and 1980s, scientists were focusing on the decoding of the genetic information – how the genome is transcribed and translated, but how proteins are degraded has remained a neglected research area. The discovery of the ubiquitin-proteasome system (UPS) with its numerous components and myriad functions has changed the paradigm that regulation of cellular processes occurs solely at the transcriptional and translational levels, and has set regulated proteolysis in a prominent position. It is now known that ubiquitin-mediated proteolysis is involved in regulating basically any cellular process, including cell cycle and division, differentiation, signal transduction, maintenance of the integrity of the genome and proteome, and the many routes the cell communicates with its environment. With the multitude of substrates targeted and processes involved, it has not been surprising to find that aberrations in the pathway have been implicated in the pathogenesis of many diseases, among them certain malignancies and neurodegenerative disorders. Consequently, the system has become a major platform for drug targeting, and several successful anti-cancer drugs are already on the market. Many more that will target also neurodegenerative and inflammatory diseases are in the pipeline. The ubiquitin system was not discovered by a screen, but rather via an attempt to answer a curiosity-driven biological question: what is the mechanism which mediates selective protein degradation? A simple proteolytic essay was set, and gradually, this most elegant, yet giant system, has started to emerge in its full beauty.  On the history of the discovery of the ubiquitin system, see Reference 1.

  1. Ciechanover, A. (2015). The Unraveling of the Ubiquitin System. Nature Rev. Mol. Cell. Biol. 16, 322-324

Our laboratory is located in the Technion’s Integrated Cancer Center (TICC) in the Rappaport Faculty of Medicine of the Technion-Israel Institute of Technology.  The Center was established in 2003 through the vision and a generous donation from David and Janet Polak.  It focused on several biological aspects of cancer, including angiogenesis, mechanisms of metastases, genetics, and the role of the ubiquitin system in the pathogenesis of the disease. We currently expand its activity to include many more aspects of this multi-faceted disease, including informatics, metabolomics, and in collaboration with the Oncology Centers in Northern Israel – to application of Precision Medicine for the benefit of cancer patients.