Death receptor 5
(Redirected from TNFRSF10B)
Death receptor 5 (DR5), also known as TRAIL receptor 2 (TRAIL-R2) or TNF-related apoptosis-inducing ligand receptor 2 (TNFRSF10B), is a protein that in humans is encoded by the TNFRSF10B gene. DR5 is a member of the tumor necrosis factor receptor superfamily and plays a crucial role in the process of apoptosis.
Structure[edit | edit source]
DR5 is a type I transmembrane protein that contains an extracellular domain, a transmembrane domain, and an intracellular death domain. The extracellular domain is responsible for binding to its ligand, TRAIL (TNF-related apoptosis-inducing ligand), while the intracellular death domain is essential for transmitting apoptotic signals.
Function[edit | edit source]
DR5 is primarily involved in the induction of apoptosis. Upon binding to TRAIL, DR5 undergoes a conformational change that allows it to recruit adaptor proteins such as FADD (Fas-associated death domain) and procaspase-8. This recruitment leads to the formation of the death-inducing signaling complex (DISC), which subsequently activates caspase-8. Activated caspase-8 then initiates a cascade of downstream caspase activation, ultimately leading to cell death.
Role in Cancer[edit | edit source]
DR5 has been extensively studied for its role in cancer biology. Many tumor cells express high levels of DR5, making them susceptible to TRAIL-induced apoptosis. This has led to the development of therapeutic agents that target DR5 to selectively induce apoptosis in cancer cells. However, some cancer cells develop resistance to TRAIL-induced apoptosis through various mechanisms, including the downregulation of DR5 expression or the upregulation of anti-apoptotic proteins.
Clinical Significance[edit | edit source]
The expression levels of DR5 can serve as a prognostic marker in certain types of cancer. High levels of DR5 expression are often associated with a better prognosis and increased sensitivity to TRAIL-based therapies. Conversely, low levels of DR5 expression can indicate resistance to such therapies and a poorer prognosis.
Research and Therapeutics[edit | edit source]
Ongoing research is focused on enhancing the efficacy of DR5-targeted therapies. Strategies include the development of agonistic antibodies that mimic TRAIL, combination therapies that sensitize tumor cells to TRAIL, and the identification of biomarkers that predict response to DR5-targeted treatments.
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External Links[edit | edit source]
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