TANK - TRAF family member-associated NF-kappa-B activator | Elisa - Clia - Antibody - Protein

Background

TRAF family member-associated NF-kappa-B activator (TANK) is a pivotal adaptor protein involved in the regulation of NF-κB signaling pathways. NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) is a critical transcription factor that controls the expression of genes involved in immune and inflammatory responses, cell survival, and proliferation. TANK functions as a scaffold protein that modulates the activity of TRAF (TNF receptor-associated factor) proteins, which are essential mediators in NF-κB signaling. By interacting with TRAF proteins, TANK helps in regulating the activation and inhibition of NF-κB pathways, thereby influencing immune responses and cellular stress reactions. Dysregulation of TANK is implicated in various pathological conditions, including autoimmune diseases, cancers, and chronic inflammatory disorders.

Protein Structure

TANK is composed of several functional domains:

• N-terminal Coiled-Coil Domain: Involved in protein-protein interactions, particularly with TRAF proteins.
• Intermediate Region: Contains multiple phosphorylation sites that are crucial for its regulatory functions.
• C-terminal Region: Facilitates interactions with other signaling proteins, including IKK (IκB kinase) complex components, influencing NF-κB signaling.

Classification and Subtypes

TANK is classified as an adaptor protein within the NF-κB signaling pathway. While there are no specific subtypes of TANK, it interacts with various TRAF family members (such as TRAF2, TRAF3, and TRAF5) and other signaling molecules, highlighting its versatile role in different signaling contexts.

Function and Biological Significance

TANK plays several critical roles in cellular processes:

• NF-κB Activation: Acts as a scaffold that facilitates the assembly of signaling complexes, leading to the activation of NF-κB. It is particularly involved in the non-canonical NF-κB pathway.
• Immune Response Modulation: By regulating NF-κB signaling, TANK influences the expression of cytokines, chemokines, and other immune-related genes, thereby modulating immune responses.
• Cell Survival and Apoptosis: TANK's role in NF-κB signaling also affects cell survival and apoptosis, with implications in both normal cellular function and disease states.
• Viral Infection Response: TANK is involved in the cellular response to viral infections by modulating the signaling pathways that lead to the production of antiviral cytokines.

Clinical Issues

Dysregulation of TANK is associated with various diseases:

• Autoimmune Diseases: Altered TANK function can lead to inappropriate activation or inhibition of NF-κB, contributing to autoimmune conditions such as systemic lupus erythematosus (SLE) and rheumatoid arthritis.
• Cancer: Abnormal TANK expression or function can influence cell proliferation and survival, contributing to oncogenesis. Its role in modulating NF-κB signaling is particularly relevant in the context of cancers such as lymphoma and leukemia.
• Chronic Inflammatory Disorders: TANK dysregulation can lead to persistent NF-κB activation, contributing to chronic inflammatory states and related diseases, including inflammatory bowel disease (IBD) and chronic obstructive pulmonary disease (COPD).

Summary

TANK (TRAF family member-associated NF-kappa-B activator) is a crucial adaptor protein in the regulation of NF-κB signaling pathways, impacting immune responses, cell survival, and inflammation. It interacts with TRAF proteins and other signaling molecules through its coiled-coil and phosphorylation-rich domains, facilitating the assembly and regulation of NF-κB signaling complexes. Dysregulation of TANK is linked to autoimmune diseases, cancers, and chronic inflammatory disorders, underscoring its importance in maintaining cellular homeostasis and its potential as a therapeutic target. Understanding the precise mechanisms of TANK function and regulation offers valuable insights into the treatment of these diseases.