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Chemical Biology Lecture: Cysteine-nitrosation affects protein ubiquitination and proteasomal proteolysis

  • Prof. Benedikt Kessler (University of Oxford)
Thursday 25 October 2018
Gorlaeus Building
Einsteinweg 55
2333 CC Leiden

It is our pleasure to announce that Benedikt Kessler from the University of Oxford will come to tell us about his most recent work on activity-based protein profiling and proteomics in the context of the ubiquitin-proteasome system.

What makes Prof. Kessler’s work unique is his combination of method and tool development with a firm embedding in biology. This has resulted in many exciting publications in which his chemical biology toolkit is used to address biological hypotheses.


Nitric Oxide (NO) is an intracellular signalling mediator, which affects many biological processes via the posttranslational modification of proteins through S-nitrosation. Using a global proteomics “biotin switch” approach, we identified components of the ubiquitin-proteasome system to be altered via NO signalling by protein S-nitrosation. We show S-nitrosation of ubiquitin conjugating E2 enzymes, such as the catalytic residue C87 of UBC13/UBE2N, leading to impaired polyubiquitylation by interfering with the formation of UBC13~Ub thioester intermediates.

In addition, proteasome cleavage activity in cells also seems to be altered by S-nitrosation, correlating with the modification of cysteine residues within the 19S regulatory particle and catalytic subunits of the 20S complex. Our results highlight the widespread impact of NO-dependent downstream cellular signalling as evidenced by the effect of the NO-Redox balance on critical processes within the ubiquitin-proteasome system (UPS). These studies thereby uncover a novel aspect of NO associated modulation of cellular homeostasis.

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