The ubiquitin/proteasome system in neurodegenerative diseases and cancer – Nico Dantuma's Group

Our major objectives are to understand the role of the ubiquitin/proteasome system in the development of neurodegenerative diseases and cancer and to explore the therapeutic potential of modifiers of this system.

People standing next to each other by a railing.
Microscopic picture of a neuronal cell

Our research

Regulated degradation of proteins in our cells is executed by the ubiquitin/proteasome system. As such the ubiquitin/proteasome system is critical for the degradation of key regulators that are implicated in signaling, regulation of the cell cycle and induction of apoptosis. Moreover, the ubiquitin/proteasome system is also important for protein quality control given its role in the destruction of abnormal, misfolded and dysfunctional proteins. Hundreds of enzymes are involved in the coordinated efforts of the ubiquitin/proteasome system in protein degradation underscoring its potential as therapeutic target for a broad variety of diseases. Tumor cells are in particularly sensitive to inhibition of the ubiquitin/proteasome system and the first proteasome inhibitor has recently been introduced in the clinic for the treatment of multiple myeloma, a type of blood cancer. Interestingly, enhancing proteasomal degradation of proteins linked to neurodegenerative diseases can reduce their toxicity.

We have developed tools to study the ubiquitin/proteasome system in cellular and animal models. Real-time imaging of fluorescently tagged proteins in living cells plays an important role in our research. These experimental approaches are used to gain insights in the functional status of the ubiquitin/proteasome system in various diseases and to decipher the molecular mechanisms that are responsible for alterations caused by disease-associated proteins. In addition, we use these models in the development of novel compounds that target the ubiquitin/proteasome system. We are also exploring the non-proteolytic role of ubiquitin in the cellular response to DNA damage.


Selected publications

Staff and contact

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