Tumor necrosis factor receptor-associated factor 4 (TRAF4) is a unique member of the TRAF protein family, which plays a pivotal role in various intracellular signaling pathways, particularly those associated with immune responses, cell survival, and development. Unlike other TRAF proteins predominantly known for their roles in immune signaling, TRAF4 exhibits distinct expression patterns and functional profiles, especially in embryonic development, epithelial cell polarity, and tumorigenesis.
Structural Features and Expression
TRAF4 contains the characteristic TRAF domain at the C-terminus, which mediates interactions with membrane-bound receptors and other signaling molecules. It also includes a RING finger domain and several zinc finger motifs that are involved in protein-protein interactions and ubiquitin ligase activity. TRAF4 is expressed broadly but shows particularly high levels in epithelial tissues and during early embryonic development. Its subcellular localization is notable—TRAF4 is found not only in the cytoplasm but also at the plasma membrane and even the nucleus under certain conditions, indicating its versatile functional roles.
Biological Functions and Signaling Pathways
TRAF4 participates in several key signaling pathways, including:
l NF-κB Pathway: While many TRAF proteins activate NF-κB, TRAF4 exhibits both activating and inhibitory effects depending on the cellular context. It modulates inflammation and immune homeostasis.
l TGF-β Signaling: TRAF4 interacts with Smad proteins and has been shown to influence TGF-β-induced transcriptional activity, which is critical in cell differentiation and fibrosis.
l Reactive Oxygen Species (ROS) Regulation: TRAF4 influences cellular oxidative stress responses and has been implicated in controlling ROS homeostasis.
l PI3K/AKT and Wnt Pathways: Emerging evidence suggests TRAF4 may crosstalk with oncogenic pathways like PI3K/AKT and Wnt/β-catenin, linking it to cancer cell proliferation and migration.
Role in Development and Disease
TRAF4 is essential for embryonic development in vertebrates. Knockout studies in mice have revealed defects in neural tube closure and epithelial organization, highlighting its role in morphogenesis.
In pathological conditions, TRAF4 is often overexpressed in various carcinomas, including breast, prostate, and lung cancers. Its upregulation is associated with enhanced metastatic potential, resistance to apoptosis, and epithelial-to-mesenchymal transition (EMT). As such, TRAF4 is being investigated as a potential prognostic marker and therapeutic target in oncology.
Moreover, alterations in TRAF4 signaling have been linked to autoimmune diseases and inflammatory disorders. However, its exact contribution remains complex and context-dependent, warranting further research.
Research and Therapeutic Potential
Given its involvement in multiple signaling axes and disease mechanisms, TRAF4 is an attractive target for drug discovery and functional studies. Current research is focused on:
l Elucidating its molecular interactome via proteomics
l Developing small-molecule inhibitors or peptides that modulate TRAF4-receptor interactions
l Using CRISPR/Cas9 and RNAi technologies to dissect its function in specific tissues and disease models
As a regulatory hub at the intersection of development, immunity, and cancer, TRAF4 represents both a challenge and an opportunity for translational research.
How to Select the Right TRAF4 Protein Product
Selecting a suitable TRAF4 protein product is essential for ensuring experimental accuracy and relevance. Here are key factors to consider:
l Species origin: Choose a TRAF4 protein that matches your experimental system—human, mouse, or rat—especially when studying species-specific interactions.
l Expression system: TRAF4 proteins can be expressed in E. coli, HEK293, or insect cells. Mammalian or baculovirus systems offer better folding and post-translational modifications, which are critical for signaling studies.
l Protein tags: Decide whether you need a His-tag, GST-tag, or tag-free version depending on your downstream application (e.g., pull-down assays, ELISA, or functional cell assays).
l Purity and validation: Look for products with >90% purity and verified activity, ideally confirmed by SDS-PAGE, Western blot, or ELISA.
l Functional relevance: For binding or signaling assays, ensure the protein includes the full-length sequence or critical domains (e.g., TRAF or RING domains).
l Storage and formulation: Consider buffer composition, storage temperature, and stability—especially if planning long-term studies.
Reputable suppliers will provide COA (certificate of analysis), sequence details, and batch-specific QC data, which are crucial for experimental reproducibility. in multiple signaling axes and disease mechanisms, TRAF4 is an attractive target for drug discovery and functional studies. Current research is focused on:
l Elucidating its molecular interactome via proteomics
l Developing small-molecule inhibitors or peptides that modulate TRAF4-receptor interactions
l Using CRISPR/Cas9 and RNAi technologies to dissect its function in specific tissues and disease models
As a regulatory hub at the intersection of development, immunity, and cancer, TRAF4 represents both a challenge and an opportunity for translational research .
Suppliers that provide TRAF4 Protein products:
Cusabio
MyBioSource
Abbexa
Thermo Fisher Scientific
NovoPro Biosciences
ProteoGenix
