Tumor necrosis factor receptor superfamily member 21 (DR6 (Death receptor 6))

Tumor necrosis factor receptor superfamily member 21 (also called Death receptor 6 or DR6) is a cell surface receptor that belongs to the tumor necrosis factor receptor superfamily.[1][2][4][5][6] It is predominantly expressed in immune organs and cells (thymus, spleen, white blood cells) as well as in the brain and endothelium. DR6 mediates apoptosis through interactions that activate NF-κB and MAPK/JNK signaling pathways and is involved in cell death both for immune regulation and neuronal development. In the immune system, DR6 modulates T-helper cell activity and cytokine release (particularly Th2 polarization) and participates in adaptive immune regulation; in the nervous system, DR6 interacts with fragments of amyloid precursor protein (APP) contributing to neuronal and axonal degeneration, which implicates it in neurodegenerative conditions like Alzheimer's disease. Clinical studies show elevated free serum DR6 levels in some cancers, such as advanced ovarian cancer, and it is considered a candidate biomarker for immune and neurodegenerative pathologies. Targeting DR6 therapeutically requires caution due to its roles in apoptosis and immune homeostasis.

Other names

Death receptor 6DR6CD358BM-018TR7

Apoptosis induction (via activation of NF-κB, JNK/MAPK8, and caspase pathways); Signal transduction through death domain (interaction with TRADD and downstream effectors); Modulation of cytokine release by T cells