#Q15843
4738
Product Information
Product Usage Information
Use as a blocking reagent to evaluate the specificity of antibody reactivity in dot blot protocols.
Storage
Product Description
Background
Neural precursor cell-expressed developmentally downregulated protein 8 (NEDD8), also known as Rub1 (related to ubiquitin 1) in plants and yeast, is a member of the ubiquitin-like protein family (1,2). The covalent attachment of NEDD8 to target proteins, termed neddylation, is a reversible, multi-step process analogous to ubiquitination. NEDD8 is first synthesized in a precursor form with a carboxy-terminal extension peptide that is removed by either the UCH-L3 or NEDP1/DEN1 hydrolase protein to yield a mature NEDD8 protein (3,4). Mature NEDD8 is then covalently linked to target proteins via the carboxy-terminal glycine residue in a reaction catalyzed by the APP-BP1/Uba3 heterodimer complex and Ubc12 as the E1- and E2-like enzymes, respectively (5). An E3 ligase protein, Roc1/Rbx1, is also required for neddylation of the cullin proteins (6). Protein de-neddylation is catalyzed by a number of enzymes in the cell, including a "ubiquitin-specific" protease USP21, the NEDP1/DEN1 hydrolase and the COP9/signalosome (CSN) (7,8,9). In contrast to the ubiquitin pathway, the NEDD8 modification system acts on only a few substrates and does not appear to target proteins for degradation. Neddylation of cullin proteins activates the SCF (Skp1-Cullin-F-box) E3 ubiquitin ligase complex by promoting complex formation and enhancing the recruitment of the E2-ubiquitin intermediate (10). While NEDD8 modification of VHL is not required for ubiquitination of HIF1-α, it is required for fibronectin matrix assembly (11). Mdm2-dependent neddylation of p53 inhibits its transcriptional activity (12).
- Chiba, T. and Tanaka, K. (2004) Curr. Protein Pept. Sci. 5, 177-184.
- Schwartz, D.C. and Hochstrasser, M. (2003) Trends Biochem. Sci. 28, 321-328.
- Wada, H. et al. (1998) Biochem. Biophys. Res. Commun. 251, 688-692.
- Hemelaar, J. et al. (2004) Mol. Cell Biol. 24, 84-95.
- Osaka, F. et al. (1998) Genes Dev. 12, 2263-2268.
- Kamura, T. et al. (1999) Genes Dev. 13, 2928-2933.
- Gong, L. et al. (2000) J. Biol. Chem. 275, 14212-14216.
- Mendoza, H.M. et al. (2003) J. Biol. Chem. 278, 25637-25643.
- Lyapina, S. et al. (2001) Science 292, 1382-1385.
- Kawakami, T. et al. (2001) EMBO J. 20, 4003-4012.
- Stickle, N.H. et al. (2004) Mol. Cell Biol. 24, 3251-3261.
- Xirodimas, D.P. et al. (2004) Cell 118, 83-97.
Species Reactivity
Species reactivity is determined by testing in at least one approved application (e.g., western blot).
Cross-Reactivity Key
H: human M: mouse R: rat Hm: hamster Mk: monkey Vir: virus Mi: mink C: chicken Dm: D. melanogaster X: Xenopus Z: zebrafish B: bovine Dg: dog Pg: pig Sc: S. cerevisiae Ce: C. elegans Hr: horse GP: Guinea Pig Rab: rabbit All: all species expected
Trademarks and Patents
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