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Dr Simon Cobbold – Ubiquitin Signalling division

31/07/2024 1:00 pm - 31/07/2024 2:00 pm
Location
Davis Auditorium

WEHI Wednesday Seminar hosted by Professor David Komander
 

Dr Simon Cobbold

Senior Research Officer – Komander Laboratory, Ubiquitin Signalling division – Healthy Development & Ageing Theme, WEHI

 

When ubiquitin and sugar meet

 

Davis Auditorium

Join via SLIDO enter code #WEHIWednesday

Including Q&A session
 

 

 

Protein ubiquitination is a prevalent post-translational modification that regulates all cellular pathways, including protein degradation, trafficking and cell signalling. Disruptions or perturbations in ubiquitin modifications can result in a wide range of human diseases and are often direct participants of neurodegeneration, inflammation and cancer.

 

Conventional ubiquitination occurs via the attachment of ubiquitin to lysine residues of substrate proteins, but several studies have convincingly shown ubiquitination of non-protein substrates such as lipopolysaccharide and lipids. These studies suggest that the substrate repertoire of ubiquitin extends beyond protein regulation.  However, the scope and role of non-proteinaceous ubiquitination remain elusive, hindered by the absence of suitable methodologies for detecting these unconventional species.

 

Here I will present the NoPro-clipping method for detection of non-proteinaceous ubiquitination. NoPro-clipping uses two complementary enzymes—a ubiquitin-clippase and a transpeptidase for labelling of ubiquitin-clipped substrates—enabling untargeted detection of non-proteinaceous ubiquitination via mass spectrometry. Using the NoPro-clipping method, ubiquitinated glycogen is detectable within cell lines under proximity-induced E3-ligase recruitment and basally in resting muscle. The presence of endogenous Ub-glycogen raises fundamental questions about its role in muscle physiology, glycogen metabolism and the mechanisms underlying a range of glycogen storage diseases. Moreover, this approach opens new avenues to explore ubiquitination of other macromolecules and their potential roles in various cellular processes and disease.

 

All welcome!

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