Death receptor 6

Death receptor 6 (DR6), also known as tumor necrosis factor receptor superfamily member 21 (TNFRSF21), is a is_associated_with::cell surface receptor of the is_associated_with::tumor necrosis factor receptor superfamily which activates the is_associated_with::JNK and is_associated_with::NF-κB pathways. It is mostly expressed in the is_associated_with::thymus, is_associated_with::spleen and is_associated_with::white blood cells.

Function
The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor has been shown to activate is_associated_with::NF-κB and is_associated_with::MAPK8/JNK, and induce cell is_associated_with::apoptosis. Through its is_associated_with::death domain, this receptor interacts with is_associated_with::TRADD protein, which is known to serve as an adaptor that mediates signal transduction of TNF-receptors. Knockout studies in mice suggested that this gene plays a role in is_associated_with::T helper cell activation, and may be involved in inflammation and immune regulation.

Clinical significance
DR6 is also thought to be involved in is_associated_with::neurodegeneration in the brain that causes is_associated_with::Alzheimer's disease as well as is_associated_with::signal transduction in stress response and cellular survival. DR6 induces apoptosis when it is over expressed, however the manner in which the death signal is intracellularly transduced is currently unknown. It has been determined that Bax translocation is necessary for the apoptosis triggered by DR6, but through an unknown pathway instead of the traditional pathways of intrinsic versus extrinsic. APP (is_associated_with::amyloid precursor protein) is the natural ligand of DR6 and is first cleaved into is_associated_with::Aβ and N-APP. N-APP is the fragment that interacts with DR6 to trigger axonal degradation in Alzheimer's patients. This pathway is essentially "hi-jacked" in the aging brain.