The enzymes of the NEDDylation pathway play a pivotal role in a number of cellular processes including the indirect regulation and targeting of substrate proteins for proteasomal degradation. Three classes of enzymes are involved in the process of NEDDylation; the ubiquitin-like activating enzyme APP-BP1/Uba3 (E1), the ubiquitin-like conjugating enzymes (E2s) and protein ligases (E3s). UBE2F is a member of the E2 conjugating enzyme family and the human gene was first described by Huang et al. (2009). UBE2F acts as a NEDD8 conjugating enzyme both in vitro and in vivo. UBE2F accepts the ubiquitin-like protein NEDD8 from the Uba3-NAE1 (APP-BP1/Uba3) E1 complex and catalyzes its covalent attachment to other proteins. The specific interaction of UBE2F with the E3 ubiquitin ligase RBX2, but not RBX1, suggests that the RBX2-UBE2F complex NEDDylates specific target proteins such as CUL5, a component of one of the many Cullin Ring Ligases (CRLs) (Huang et al., 2009).
Huang DT, Ayrault O, Hunt HW, Taherbhoy AM, Duda DM, Scott DC, Borg LA, Neale G, Murray PJ, Roussel MF, Schulman BA (2009) E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification. Mol Cell 33, 483-95.