Conjugation of mature NEDD8 to specific lysine residues on target proteins via isopeptide bonds allows NEDD8 to play a critical regulatory role in cell proliferation and development, a process closely associated to the ubiquitin-proteasome pathway. An increasing number of substrates for NEDDylation are being identified including the tumor suppressors p53 and VHL and members of the well-characterized cullin ubiquitin E3 ligase family, underlining the vital role NEDD8 modification plays in cellular processes.
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