Nedd4-1 is an E3 ubiquitin ligase that contains a C2 domain, three or four WW domains, and a ubiquitin ligase Hect domain, and it belongs to the Nedd4 family of Hect E3 ligases that also includes its relative Nedd4-2 (1, 2). The WW domain of Nedd4 proteins recognizes and binds a short amino acid sequence in substrate proteins, called the PY motif (L/PPxY) (3, 4). PTEN is a tumor suppressor protein that frequently exhibited mutations and it is suggested that PTEN stability and sub-cellular distribution is mediated by E3 ubiquitin ligase Nedd4. In most of the cancers the PTEN, a critical regulator of multiple cellular processes is either mutated or deleted and these changes have profound impacts on carcinogenesis. The Nedd4 negatively regulated PTEN stability by catalyzing PTEN ubiquitination via Nedd4. The ubiquitin ligase Nedd4 has been proposed to regulate a number of signaling pathways, but its physiological role in mammals has not been characterized. Nedd4 knockout mouse exhibited reduced insulin-like growth factor 1 (IGF1) and insulin signaling, delayed embryonic development, reduced body weight neonatal lethality, embryonic fibroblasts mitotic activity is reduced and the Nedd4 adapter protein grb10 is increased (5).
Nedd4 has at least 2 homologues, Nedd4-1 and Nedd4-2, the human genomic loci of these two homologues are different (Nedd4-1 is on 15q21 and 18q21 for Nedd4-2). Only the Nedd4-1 was found associated with ubiquinated PTEN while Nedd4-2 has no ubiquitin ligase activity (6). Nedd4-1 is 887 amino acids long with approximately 115kDa protein abundantly found in HeLa S100 cells. Mouse Nedd4-2 is slightly larger in size with 1004 amino acids.
The Nedd4-101AP-selective rabbit antibodies were generated against a common epitope present in both Nedd4-1 and Nedd4-2 protein near the C-terminal end of the protein. The synthetic peptide was covalently modified to achieve desired antigenic properties and was conjugated to a carrier protein before used as immunogen to raise antibodies. The Nedd4 antibodies are affinity purified over immobilized immunogenic peptide affinity matrix and stabilized with preservatives for long-term storage. FabGennix will conjugate this antibody to secondary enzymes (alkaline phosphatase or horseradish peroxidase) and fluorophores at a nominal charge. FabGennix Int. Inc. stocks limited quantities of western blot positive controls for Nedd4 in ready-to-use buffers and antigenic blocking peptide for immune-depletion assays for Nedd4-101AP antibody. FabGennix Int. Inc., has a wide range of antibodies and reagents for biomedical research community. For a complete listing please visit www. FabGenix.Com. FabGennix Inc. will also conjugate antibodies with fluorescent/enzymatic probes upon request at a reasonable cost.
For research use only, not for diagnostic or therapeutic use.
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