NEDP1, a human NEDD8-specific protease, is highly conserved throughout evolution and equivalent proteins are present in yeast, plants, insects, and mammals. NEDP1 appears to be specific for NEDD8 as neither ubiquitin nor SUMO bearing COOH- terminal extensions are utilized as substrates. Inhibition studies and mutagenesis indicate that NEDP1 is a cysteine protease with sequence similarities to SUMO-specific proteases and the class of viral proteases typified by the adenovirus protease. in vivo NEDP1 deconjugates NEDD8 from a wide variety of substrates including the cullin component of SCF-like complexes. Thus NEDP1 is likely to play an important role in ubiquitin-mediated proteolysis by controlling the activity of SCF complexes.
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