Introduction

Ubiquitination, conjugation of protein with the 76-amino acid ubiquitin, is one of the most common forms of post-translational modification in eukaryotic cells. A well-known function of ubiquitination is targeting proteins to proteasome, a multi-subunits proteolytic complex. The ubiquitin proteasome system constitutes a major protein degradation pathway that controls the level and quality of proteins. Emerging evidence indicates that ubiquitination also has many non-degradative functions through directly affecting the activities and intracellular locations of modified proteins. Therefore, ubiquitination is involved in numerous cellular processes from DNA repair and signal transduction to cell cycle and apoptosis. Alterations of ubiquitination are observed in many pathological conditions including various cancers, where its aberrations are closely related to the reduction of tumor suppressors and overexpression of oncogenes.

Ubiquitin E1

Ubiquitin E1

Ubiquitination is catalyzed by the sequential action of at least three enzymes, ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin protein ligase (E3). E1 activates ubiquitin and forms a thioester conjugate with activated ubiquitin, which is then transferred to E2. E3 interacts with both E2 and specific substrate, catalyzing the formation of an isopeptide bond between the C-terminal glycine of activated ubiquitin and the -amino group of a lysine in the target protein. In mammalian cells, there are more than 30 different E2s and hundreds of E3s, but only one essential E1. Therefore, E1 is the only common step in the ubiquitination process. While proteasome inhibitor prevents the degradative function of ubiquitination, E1 inhibitor blocks both degradative and non-degradative functions of the ubiquitin proteasome system and thus is a valuable tool for exploring the biological roles of ubiquitination.

logo_forcopy offers the FIRST ubiquitin E1 inhibitor to the ubiquitination research field. Contact Us