Antibodies for Proteasome Research

A vast majority of short-lived proteins are degraded by the ubiquitin-proteasome pathway. A protein marked for degradation is covalently attached to multiple molecules of ubiquitin, a
highly conserved 76-amino acid (8.6 kDa) protein, by a multi-enzymatic system consisting of Ubiquitin-activating (E1), Ubiquitin-conjugating (E2), and the Ubiquitin-ligating (E3) enzymes. The E1 enzymes activates a Ubiquitin monomer at its C-terminal cysteine residue to a high-energy thiolester bond which is then transferred to a reactive cysteine residue of the E2 enzyme. The final transfer of ubiquitin to the e-amino group of a reactive lysine residue of substrate proteins is brought about by the E3 enzyme. Ubiquitinated protein is then escorted to the 26S proteasome where it undergoes final degradation and the ubiquitin is released and recycled. Protein degradation in the Ubiquitin-proteasome pathway plays an important role in cell cycle, signal transduction, and in maintaining the structural integrity of the protein.