WEHI PhD Completion Seminar hosted by Dr Bekky Feltham

Tamer Aly

PhD Student – Feltham Laboratory, Ubiquitin Signalling division, WEHI

When E2s Take Control: Self-Regulation Through E3-Independent Auto-Ubiquitination

 

Davis Auditorium

Join via SLIDO enter code #WEHIphdcompletion

Including Q&A session

Followed by refreshments in Tapestry Lounge

Ubiquitination is a post-translational modification that regulates protein stability, activity, and localisation, making the ubiquitin system a fundamental cellular regulatory mechanism. Protein ubiquitination occurs through a tightly regulated enzymatic cascade involving E1 ubiquitin activating, E2 ubiquitin conjugating, and E3 ubiquitin ligase enzymes.

Traditionally, E2s have been regarded as mere middlemen, simply carrying ubiquitin from the E1 to the E3. However, sitting at the heart of the ubiquitination cascade, E2s have been elucidated to control many aspects of the ubiquitination process which dramatically alters the outcomes of ubiquitination.

During my PhD, I used a combination of mass spectrometry, in vitro, and cell and molecular biology approaches to study the regulation of E2s. We investigated an internal ubiquitination site, conserved in 25% of human E2s, which is adjacent to the E2s’ catalytic cysteine. We show that this site is autoubiquitinated in an E3 ligase-independent manner and can modulate the outcome of the E2/E3 interaction which alters the rate of ubiquitin chain assembly. We further demonstrate that this site influences cellular response to inflammatory stimuli whose initiation is dependent on ubiquitination.

This work advances our understanding of E2s, central players in the ubiquitin system whose regulation is essential for maintaining cellular homeostasis.

All welcome!