Ubiquitin Proteasome Pathway

All eukaryotic cells have a very complex and tightly regulated process for maintaining cellular protein quality. Such a well-regulated protein turnover system is crucial to the sustenance of a variety of basic cellular processes including maintenance of cellular protein homeostasis. The Ubiquitin proteasome pathway, also called UPS (Ubiquitin Proteasome System) is conserved from yeast to mammals and required for the targeted degradation of most short-lived proteins in the eukaryotic cell. UPS allows the cell to quickly adapt and reprogram the protein pool to function at its most efficient under any nutritional or physiological challenge (nutrient deprivation, DNA damage, unfolded protein response due to protein overload, viral attack etc.). UPS comprises of a complicated cascade of events starting from recognition of a damaged/aberrant (folded improperly or non-functional) protein followed by tagging of the recognized substrate protein with Ubiquitin (an 8.5 kDa protein) by a system of enzymes (Ubiquitin-activating, -conjugating and -ligating enzymes also known as E1, E2 and E3 respectively) ultimately culminating in the degradation/lysis of the protein by the 26S proteasome. Typically 4-20 ubiquitin molecules (polyubiquitination) are attached to a Lysine residue on the substrate protein thus resulting in a cellular flag that targets this protein for downstream degradation processes. With the huge repertoire of substrates that are targeted for degradation through this pathway and the complicated coordinated processes involved at every step, aberrations in this pathway are implicated in the pathogenesis of many diseases including cancer, various degenerative diseases particularly those stemming from protein aggregation issues (Alzheimer's, Parkinson's etc.) thus making this pathway a focal point for designing cures to human diseases. Various important proteins involved in xenobiotic metabolism such as drug transporters like P-glycoprotein, some Cytochrome P450 enzymes are turned over via UPS thus making it fundamentally important to understanding and modulating drug clearance.

BioVision's catalog boasts an extensive collection of inhibitors targeting various proteins/enzymes functioning at various steps of the Ubiquitin Proteasome Pathway.

Ubiquitin Proteasome Pathway Subcategories