MYD88

What is MYD88 protein?

MYD88 gene (MYD88 innate immune signal transduction adaptor) is a protein coding gene which situated on the short arm of chromosome 3 at locus 3p22. This gene encodes a cytosolic adapter protein that plays a central role in the innate and adaptive immune response. This protein functions as an essential signal transducer in the interleukin-1 and Toll-like receptor signaling pathways. These pathways regulate that activation of numerous proinflammatory genes. The encoded protein consists of an N-terminal death domain and a C-terminal Toll-interleukin1 receptor domain. The MYD88 protein is consisted of 296 amino acids and MYD88 molecular weight is approximately 33.2 kDa.

What is the function of MYD88 protein?

The MYD88 protein is a vital adaptor molecule in the immune system, primarily involved in the signaling pathways of Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs). It plays a crucial role in mediating inflammatory responses to pathogens by relaying signals that activate transcription factors like nuclear factor-kappa B (NF-κB) and various mitogen-activated protein kinases (MAPKs), leading to the production of proinflammatory cytokines.

MYD88 related signaling pathway

The MYD88-related signaling pathway is a critical component of the innate immune response, playing a central role in mediating signaling downstream of Toll-like receptors (TLRs) and IL-1 receptor (IL-1R). Upon activation by microbial ligands or cytokines, MYD88 facilitates the recruitment and activation of downstream kinases such as IRAK, leading to the activation of NF-κB and MAPK pathways. This results in the expression of pro-inflammatory cytokines and chemokines, which are essential for host defense against infections. Dysregulation of this pathway is implicated in various inflammatory diseases and certain types of cancer.

MYD88 related diseases

MYD88-related diseases encompass a range of conditions primarily driven by dysregulation of the innate immune response. Central to these diseases is the overactivation of the MYD88 signaling pathway, which plays a crucial role in mediating inflammation through Toll-like receptors (TLRs) and IL-1 receptor (IL-1R). This leads to an excessive and prolonged inflammatory response that can result in autoimmune disorders such as rheumatoid arthritis, Crohn's disease, and lupus. Additionally, mutations in MYD88 are associated with an increased risk of certain malignancies, including lymphomas and leukemias. Therapeutic strategies targeting MYD88 or its downstream pathways are being actively pursued to manage these conditions effectively.

Fig1. The TLR/MyD88/NF-κB signalling pathway and target regions for designing MyD88 inhibitors. (Meiqi Liu, 2023)

Bioapplications of MYD88

The MYD88 protein is a central adapter molecule in the immune system's signaling pathways, primarily involved in the cascade of events initiated by Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs). It coordinates the innate immune response and helps establish the adaptive immune response. By activating various signaling pathways such as nuclear factor-κB (NF-κB) and activator protein-1 (AP-1), MYD88 promotes the production of immune and inflammatory mediators. In the context of bioapplications, MYD88 is a promising therapeutic target for diseases like neuroinflammation, acute liver/kidney injury, autoimmune diseases such as systemic lupus erythematosus, and B-cell lymphoma with the MyD88 L265P mutation. The development of specific inhibitors like ST2825 suggests potential therapeutic value in modulating host immune regulation for inflammatory diseases and therapies.