Seminar: Dr. Huib Ovaa

Chemistry of ubiquitination, proteolysis and antigen presentation

Date:
20 August 2013 00:00 hrs.
Location:
Figdor Lecture Theatre, 8th floor RIMLS Building, Geert Grooteplein 26-28, route 289
Title:
Chemistry of ubiquitination, proteolysis and antigen presentation
Speaker(s):

Dr. Huib Ovaa, Netherlands Cancer Institute (NKI), Division of Cell Biology II

Host(s):

Dr. Martijn Verdoes, Department of Tumor Immunology, NCMLS

20-08-2013 00:00:00Europe/AmsterdamChemistry of ubiquitination, proteolysis and antigen presentation Figdor Lecture Theatre, 8th floor RIMLS Building, Geert Grooteplein 26-28, route 289Rimlsrimls@radboudumc.nl

Remarks / more information:

Ovaa , HuibCellular protein degradation and many other cellular processes are controlled by post-translational modification of proteins with ubiquitin. Ubiquitin itself is a small protein that consists of 76 amino acids and ubiquitin modification is tightly controlled by many enzymes. Approximately 1,000 enzymes exist that are responsible for ubiquitin conjugation and 100 deubiquitinating enzymes are encoded in the human genome that reverse ubiquitin modification. Malfunction of several of these components that control ubiquitination frequently are associated with cancer. When specific ubiquitin modifications target for protein destruction, the proteasome can recognize these signals and destroy ubiquitin-tagged proteins. In this manner misfolded or redundant proteins are removed. Viral and tumor proteins are also destroyed by the proteasome and protein fragments can be presented to the immune system to indicate cancer of infection. These protein fragments are loaded into major histocompatibility class I complexes that present these antigens to cytotoxic T-cells that can subsequently eliminate infected or tumor cells.

In this lecture I will show: 1. how ubiquitin conjugates can now be synthesized by total synthesis. 2. how new chemical tools allow us to study proteasome activity; and 3. How chemical methods facilitate the study of T-cell reactivity.



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