Ubiquitin-Conjugating Enzyme E2F (UBE2F) is a member of the NEDD8-conjugating enzyme family, playing a crucial role in the neddylation pathway. This pathway is essential for the post-translational modification of proteins, which can alter their activity, stability, and localization within the cell. UBE2F is a human recombinant protein, meaning it is produced through recombinant DNA technology, typically in a bacterial or yeast expression system.
UBE2F is a 185 amino acid protein with a predicted molecular weight of approximately 21 kDa . It shares a high degree of sequence identity with its orthologs in other species, such as mice and rats, indicating its evolutionary conservation and importance . The enzyme consists of a conserved E2 catalytic core domain, which is essential for its function in transferring NEDD8 to target proteins .
The neddylation pathway involves the covalent attachment of NEDD8, a ubiquitin-like protein, to substrate proteins. This process begins with the activation of NEDD8 by an E1 NEDD8-activating enzyme, followed by its transfer to an E2 NEDD8-conjugating enzyme, such as UBE2F . Finally, an E3 NEDD8 ligase facilitates the transfer of NEDD8 from the E2 enzyme to the target protein . This modification can regulate various cellular processes, including protein degradation, signal transduction, and cell cycle progression.
UBE2F is particularly important for the neddylation of cullin proteins, which are components of cullin-RING E3 ubiquitin ligases (CRLs). These ligases play a critical role in ubiquitin-mediated protein degradation, a process essential for maintaining cellular homeostasis . By neddylating cullin proteins, UBE2F helps regulate the activity of CRLs, thereby influencing the degradation of various substrate proteins .
The neddylation pathway, and UBE2F in particular, has been implicated in various diseases, including cancer. Overactivation of the neddylation pathway can lead to the stabilization of oncogenic proteins and the degradation of tumor suppressor proteins, promoting tumorigenesis . As a result, UBE2F and other components of the neddylation pathway are being explored as potential therapeutic targets for cancer treatment .