What is NEDD4 Protein

What is NEDD4 Protein?

NEDD4, a member of the HECT (Homologous to E6-AP Carboxyl Terminus) family of ubiquitin ligases, plays a pivotal role in maintaining cellular homeostasis through its involvement in protein turnover and degradation. Structurally, NEDD4 comprises several domains, including the C2 domain for calcium-dependent lipid binding, WW domains facilitating protein-protein interactions, and the catalytic HECT domain responsible for ubiquitin transfer.

The Function of NEDD4 Protein

NEDD4's primary function lies in its role as a ubiquitin ligase, orchestrating the addition of ubiquitin molecules to specific proteins. This ubiquitination process serves multiple purposes within the cell. One of the central functions of NEDD4 is the regulation of protein degradation. By attaching ubiquitin to target proteins, NEDD4 marks them for recognition and subsequent degradation by the proteasome, ensuring the removal of damaged or unnecessary cellular components.

Moreover, NEDD4 is involved in the regulation of various cellular processes, including endocytosis, receptor internalization, and vesicle trafficking. The WW domains of NEDD4 play a crucial role in interacting with proline-rich motifs in target proteins, facilitating the ubiquitination and subsequent sorting of these proteins to specific cellular compartments.

NEDD4-Related Diseases

Given its involvement in fundamental cellular processes, dysregulation of NEDD4 has been linked to several diseases. Neurological disorders, such as Parkinson's disease, have been associated with alterations in the NEDD4 protein. Studies have shown that NEDD4 is involved in the degradation of proteins implicated in neurodegenerative diseases, highlighting its significance in maintaining neuronal health.

Additionally, NEDD4 has been implicated in cancer progression. The dysregulation of NEDD4 expression has been observed in various cancer types, influencing the stability and activity of proteins involved in cell cycle regulation and tumor suppression. Understanding the role of NEDD4 in cancer may pave the way for the development of targeted therapies aimed at modulating its activity.

NEDD4 Related Signaling Pathways

The intricate web of signal pathways in which NEDD4 participates further emphasizes its significance in cellular regulation. One notable pathway is the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR pathway. NEDD4 has been shown to interact with and regulate key components of this pathway, influencing cell growth, survival, and metabolism.

In the context of the PI3K/Akt/mTOR pathway, NEDD4's ubiquitin ligase activity targets proteins like PTEN (Phosphatase and Tensin Homolog), a tumor suppressor that negatively regulates the pathway. By ubiquitinating PTEN, NEDD4 promotes its degradation, leading to the activation of the PI3K/Akt/mTOR pathway and subsequent cellular responses.

NEDD4's role in the regulation of the transforming growth factor-beta (TGF-β) pathway is another significant aspect of its involvement in signal transduction. NEDD4 has been shown to interact with and ubiquitinate Smad proteins, key mediators of TGF-β signaling. This interaction modulates the activity of the TGF-β pathway, influencing cellular processes such as proliferation, differentiation, and apoptosis.

Figure 1. The proposed role of NEDD4 in IGF-1R signalling. (Boase, N.A., et al. 2014)

Applications of NEDD4 in Biomedical Research

The intricate involvement of NEDD4 in cellular processes and its association with diseases make it an attractive target for biomedical research and therapeutic development. Several potential applications of NEDD4 in the field of biomedicine have emerged.

1. Cancer Therapeutics

Given the role of NEDD4 in cancer progression, targeting this protein has become a potential avenue for cancer therapeutics. Small molecules or peptides that modulate NEDD4 activity could be developed to influence the stability of proteins involved in cancer pathways, providing a novel approach for cancer treatment.

1. Neurological Disorders

Understanding the role of NEDD4 in neurodegenerative diseases opens up opportunities for the development of therapies targeting this protein. Modulating NEDD4 activity could potentially influence the degradation of proteins associated with neurological disorders, offering a new avenue for therapeutic intervention.

1. Regulation of Signaling Pathways

NEDD4's involvement in key signaling pathways makes it a potential target for the regulation of these pathways. Developing compounds that selectively modulate NEDD4's interaction with specific pathway components could provide a tool for fine-tuning cellular responses and addressing aberrant signaling in various diseases.

1. Drug Discovery

NEDD4's role in protein ubiquitination and degradation makes it an attractive target for drug discovery efforts. High-throughput screening for compounds that selectively influence NEDD4 activity could lead to the identification of novel drug candidates for a range of diseases.

The NEDD4 protein emerges as a crucial player in cellular regulation, influencing diverse processes from protein degradation to signal transduction. Its involvement in diseases such as cancer and neurological disorders underscores its significance in biomedical research. Understanding the structure, function, and signal pathways associated with NEDD4 not only deepens our knowledge of fundamental cellular processes but also opens up exciting possibilities for therapeutic interventions in various diseases. As researchers continue to unravel the complexities of NEDD4, the potential for innovative treatments and targeted therapies in the realm of biomedicine continues to expand.

Recommended Products for NEDD4 Protein

Cat.#	Species	Product name	Source (Host)	Tag
NEDD4-01H	Human	Active Recombinant Human NEDD4 protein, His-tagged	E.coli	His
NEDD4-29278TH	Human	Recombinant Human NEDD4, FLAG-tagged	Insect Cell	Flag
NEDD4-520H	Human	Recombinant Human NEDD4, FLAG-tagged	Sf9 Insect Cell	Flag
NEDD4-1252H	Human	Recombinant Human NEDD4, GST-tagged	E.coli	GST
NEDD4-1245H	Human	Recombinant Human NEDD4 protein, GST-tagged	E.coli	GST
NEDD4-14H	Human	Active Recombinant Human NEDD4 Protein (Leu570-Asp1319), N-6×His-tagged	Insect Cell	N-6×His
NEDD4-4676H	Human	Recombinant Human NEDD4 Protein (Met1-Asp900), N-GST tagged	E.coli	N-GST
NEDD4-2461H	Human	Recombinant Human NEDD4 protein, His-tagged	E.coli	His
Nedd4-4359M	Mouse	Recombinant Mouse Nedd4 Protein, Myc/DDK-tagged	HEK293T	Myc/DDK

Reference

• Boase, N.A., Kumar, S. NEDD4: The founding member of a family of ubiquitin-protein ligases. Gene. 2015, 557(2): 113-22.