DEN1DEN4

DEN1DEN4 is a protein complex that plays a crucial role in the innate immune response to bacterial infections. The complex is composed of two proteins, DEN1 and DEN4, which are essential for the activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. The NLRP3 inflammasome is a multiprotein complex that senses danger signals and activates caspase-1, leading to the maturation and secretion of pro-inflammatory cytokines such as interleukin-1 beta (IL-1β) and interleukin-18 (IL-18).

DEN1DEN4 is recruited to the inflammasome by the protein ASC (apoptosis-associated speck-like protein containing a CARD), which binds to the CARD (caspase recruitment domain) of DEN1. Once recruited, DEN1DEN4 interacts with the CARD of NLRP3, facilitating the assembly of the inflammasome. The activation of the NLRP3 inflammasome by DEN1DEN4 is critical for the host defense against bacterial infections, as it leads to the production of pro-inflammatory cytokines that recruit immune cells and promote the clearance of pathogens.

DEN1DEN4 is also involved in the regulation of cell death and autophagy. It has been shown to promote necroptosis, a form of regulated necrosis, and to inhibit autophagy, a process by which cells degrade and recycle damaged organelles. The regulation of cell death and autophagy by DEN1DEN4 is thought to be important for the host response to bacterial infections, as it allows the host to balance the need for immune activation and tissue repair.

DEN1DEN4 is a promising target for the development of therapeutic strategies for the treatment of bacterial infections and inflammatory diseases. The activation of the NLRP3 inflammasome by DEN1DEN4 is a key step in the pathogenesis of several inflammatory diseases, including rheumatoid arthritis, Crohn's disease, and psoriasis. Therefore, inhibiting the recruitment of DEN1DEN4 to the inflammasome or blocking its interaction with NLRP3 may provide a new approach for the treatment of these diseases.