Spotlight: Live Webinar

Ubiquitination, E3 Ligases, and Drug Discovery:
Novel Technologies and Services for a Challenging Pathway
Register to attend our webinar to hear Dr. Neil Wilkie discuss recent breakthroughs in drug discovery within the challenging ubiquitin-proteasome pathway.
Neil Wilkie, Ph.D.
Chief Scientific Officer
UB Pharma Ltd
Ubiquitination / Proteasome Pathway in Drug Discovery and Safety Pharmacology
The ubiquitination pathway is most recognized for its role in marking proteins to be degraded through the proteasome. Dysregulation of this pathway has been associated with a number of difficult to treat diseases, like cancer and Parkinson’s disease.

The therapeutic potential of the pathway was demonstrated when the FDA approved the proteasome inhibitor bortezomib (Velcade®; Millennium Pharmaceuticals, Inc.) for the treatment of multiple myeloma in 2003. The ubiquitination pathway enzymes (i.e., E1, E2 and E3) are thought to be promising next generation targets to develop more specific therapeutics.

Millipore has removed the complexity of ubiquitination by providing functional E3 ligase cascades, making the target class readily accessible for drug discovery.


Ubiquitination/Proteasome Pathway
The ubiquitination pathway consists of three sequential steps: 1) An ATP dependent step of loading E1 activating enzyme with ubiquitin, 2) Transfer of the E1’s ubiquitin to an E2 conjugating enzyme and 3) the E3 ligase mediated transfer of ubiquitin from an E2 to the substrate. This process can be repeated to poly-ubiquinate a substrate, leading to its proteasome-mediated degradation, whereas mono-ubiquitinatinated targets (e.g., cell surface receptors) will have altered signaling properties.