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In terms of our prominent High-Affi™ technology, Creative Biolabs is able to provide customized neddylation-specific antibody with high specificity and affinity. Antibodies are produced with a synthetic peptide corresponding to amino acids of the NEDD8 protein. This antibody detects endogenous levels of both free and conjugated NEDD8 protein. Meanwhile, cross-reaction with other ubiquitin family members is avoided.
Neddylation is a process by which the ubiquitin-like protein NEDD8 (neural-precursor-cell-expressed developmentally down-regulated 8) is conjugated to its target proteins. This process includes NEDD8 precursor processing, activation by the E1 (UBA3-APPBP1 heterodimer), loading onto the E2 (Ubc12), conjugation to a substrate by an E3 and recycling of NEDD8 by an isopeptidase, which is analogous to ubiquitination. In contrast to the ubiquitination, the neddylation does not target proteins for degradation, rather acts on only a few substrates. Cullin family members are known physiological substrates of neddylation and the modification makes cullin proteins play a major role in the regulation of cell proliferation. Neddylation regulates many biological processes, including cell cycle progression and signal transduction. Aberrant modification of neddylation causes tumorigenesis given that NEDD8 is overexpressed and Cullin-RING ligases (CRLs) are abnormally activated in many human cancers. It appears to be an attractive anticancer approach to target protein neddylation, in particular the cullin neddylation. It is also found that neddylation is involved in the pathogenesis of Alzheimer's diseases (AD). NEDD8 localization is changed in AD, like NEDD8 transferring from nucleus to cytoplasm in AD hippocampal neurons.
Fig. 1 Schematic representation of the main steps of the neddylation pathway. (Rabut and Peter 2008)
Neddylation can achieve the followings by remodeling the three-dimensional surface of substrates:
A) Induce conformational changes (neddylation of cullins allows their C-terminal domain and Rbx1 to adopt catalytically active conformations);
B) Preclude association with certain partners or compete with other post-translational modifications (cullin neddylation is incompatible with CAND1 interaction);
C) Provide a novel binding surface to recruit new partners (neddylated EGFR might recruit endocytic proteins such as Eps15 or Hrs).
Fig. 2 Direct effects of neddylation. (Rabut and Peter 2008)
The antibodies against NEDD8 protein produced by Creative Biolabs via High-Affi™ technology are applicable in various immunoassays. Meanwhile, excellent results of immunoassay proved our neddylation-specific antibodies are highly specific. We can also provide custom services for unique neddylation-specific antibody discovery according to our customers’ requirements.
In addition to the neddylation-specific antibody, Creative Biolabs also provides a comprehensive list of PTM-specific antibody production services of your choice.
|Glycosylation||ISGylation||Tyrosine sulfation||Tyrosine nitration|
Fatty Acylation (N-Myristoylation,
Rabut G and Peter M. (2008). “Function and regulation of protein neddylation. 'Protein modifications: Beyond the usual suspects' review series”. EMBO Rep, 9(10): 969-976.
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