UBE2S (D5H9H) Rabbit mAb #11878

Protein ubiquitination requires the concerted action of the E1, E2, and E3 ubiquitin-conjugating enzymes. Ubiquitin is first activated through ATP-dependent formation of a thiol ester with ubiquitin-activating enzyme E1. The activated ubiquitin is then transferred to a thiol group of ubiquitin-carrier enzyme E2. The final step is the transfer of ubiquitin from E2 to an ε-amino group of the target protein lysine residue, which is mediated by ubiquitin-ligase enzyme E3 (1).
The human anaphase promoting complex (APC/C) is a large macromolecular E3 ligase complex that is largely responsible for timely progression through mitosis via the sequential targeting of cell cycle regulators for proteasomal degradation. Recent work has revealed that APC/C substrates are marked for proteasomal degradation during cell cycle progression through the covalent assembly of Lys11-linked ubiquitin chains, which occurs through a priming phase and an elongation phase (2-5). The APC/C utilizes, in part, the UBE2C/UBCH10 E2 enzyme to prime substrates for degradation through the covalent attachment of short Lys11-linked chains (3,6). The Lys11-specific elongating E2 enzyme, UBE2S/E2-EPF, extends these short chains into long Lys11-linked ubiquitin chains on APC/C bound substrates (2,3,7). In addition to the well-established biochemical role for UBE2S in cell cycle regulation, researchers have found evidence that this enzyme is overexpressed in many types of human cancer (8), and has been implicated in hypoxia signaling (9,10). Indeed, UBE2S has been reported by researchers to associate with VHL and to target it for proteasomal degradation, thereby stabilizing HIF-1α (9).