Death-associated protein 3 (DAP3) is crucial for promoting apoptosis induced by various stimulations. This report demonstrates that DAP3 is also important for T cell receptor (TCR)-mediated apoptosis induction in immature thymocytes. Enforced expression of DAP3 accelerated the negative selection in developing thymocytes, using the reaggregate thymus organ culture system. In addition, expression of DAP3 accelerated TCR-mediated apoptosis induction in DO11.10 cells. We also demonstrated that DAP3 translocates into the nucleus during TCR-mediated apoptosis in a Nur77 dependent manner. It is concluded that DAP3 is critical for TCR-mediated induction of apoptosis at the downstream of Nur77.
Negative selection is a quite important event for acquisition of self-tolerance by elimination of self-reactive thymocytes [1], [2]. During T cell development, immature CD4+CD8+ thymocytes undergo negative selection events based on the specificities of the αβT cell receptor (TCR) complexes.
Death-associated protein 3 (DAP3) is ubiquitously expressed in various tissue including the immune system, such as in the thymus of human and mice [3], [4]. DAP3 is a GTP-binding protein that has been identified as a positive mediator in interferon (IFN)-γ-induced cell death [5]. The gene of DAP3 encodes for a 46 kDa protein with a potential P-loop motif, a potential nuclear receptor-interacting domain (NR box), and a putative cleavage site for the N-terminal mitochondrial t
Death-associated protein 3 (DAP3) is a mitochondrial protein involved in apoptosis. This 2010 study investigated its specific role in T cell receptor (TCR)-mediated programmed cell death.
DAP3 was found to be critically important for TCR-mediated apoptosis in T cells. The protein functions as a GTPase and is required for efficient apoptosis signaling through the intrinsic mitochondrial pathway when T cells receive apoptotic signals through their antigen receptors. This mechanism is important for immune tolerance and preventing autoimmunity.
T cell apoptosis mechanisms are fundamental to immune regulation. Beta glucan immunomodulation influences the balance between T cell activation and apoptosis, potentially affecting immune responses in ways relevant to both cancer immunology and autoimmune disease management.
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Tosa N., Iwai A., Tanaka T., Kumagai Y., Onizuka S., Kanda T., Kikukawa T.. Critical function of death-associated protein 3 in T cell receptor-mediated apoptosis induction. Biochemical and Biophysical Research Communications. 2010. DOI: 10.1016/j.bbrc.2010.04.018.
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