The Ubiquitin Pathway

Protein targeting by ubiquitin requires sequential action of three enzymes: Ub is activated by a specific activating enzyme (E1) to yield a Ub-E1-thiolester. Activated Ub is transferred to a carrier protein (E2), and then transferred to a ligase (E3) and linked by an isopeptide bond to the substrate protein. After linkage of Ub to the substrate, a polyUb chain is usually formed. Ubiquitylated proteins can be deubiquitylated by specific isopeptidases or recognized and processed by the 26S proteasome. Proteasomes also contain Ub isopeptidase [deconjugating] activity that allows Ub recycling.

Ubiquitin Proteasome System HD

The Ubiquitin Pathway in Drug Discovery

Deubiquitylating enzymes (DUBs) and ubiquitin E3 ligases control cellular signal transduction pathways and offer promise for treating cancer, cardiovascular disease, inflammation, CNS disorders, and other diseases.  Small molecule modulators of these enzymes are now in clinical trial or poised to enter the clinic, and Progenra is contributing to the momentum in ubiquitin based therapeutics by developing novel first in class medicines. Our world-class ubiquitin technology is complemented internally by unsurpassed biology applied to both target validation and pharmacological proof of concept, and by a strong medicinal chemistry team. In addition, we maintain collaborations with leading academic laboratories in the ubiquitin field, providing us with the latest thinking on the ubiquitin-proteasome pathway.