Prof Danny Huang - Ubiquitin Signalling


Huang head 069

Post-translational modifications of ubiquitin and ubiquitin-like proteins (Ubls) control myriad of cellular processes ranging from cell cycle regulation, transcription and DNA repair to virus budding. Ubls are attached to protein targets by a hierarchical cascade of enzymes involving an E1 activating enzyme, an E2 conjugating enzyme, and an E3 ligase.

Defects in these pathways have been associated with diseases such as cancer, neurodegenerative disorder and viral infection. Bortezomib (Velcade) targets ubiquitin-proteasome system, is presently approved for treating multiple myeloma demonstrating the importance of the ubiquitin-proteasome pathway in anti-cancer therapies.

E3s promote transfer of Ub from E2 to the amino group of a substrate lysine, and thus play a pivotal role in determining substrate fate. In general, E3s contain an E2 binding module (HECT, RING, U-box and RING-in-between-RING) and a substrate-binding domain to facilitate Ub transfer. RING E3s are the largest class with ~600 members in the human genome. Our group applies X-ray crystallography and biochemical approaches to study the regulation, mechanistic functions and mutation-induced deregulation in RING E3s.

See more about Prof Huang's work on Cbl on the Protein Data Bank website.

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