What are ubiquitination signals?
Ubiquitination regulates pattern-recognition receptor signaling that mediates both innate immune responses and dendritic cell maturation required for initiation of adaptive immune responses. Deregulated ubiquitination events are associated with immunological disorders, including autoimmune and inflammatory diseases.
What is receptor ubiquitination?
Ubiquitination of signaling cell surface receptors is a key mechanism regulating the availability of these receptors to interact with extracellular ligands. Accordingly, this regulation determines the sensitivity of cells to the humoral and locally secreted regulators of cell function, proliferation, and viability.
How does TRAF 6 get ubiquitinated?
Mechanistically, in response to various pro-hypertrophic stimuli, the activation of NADPH oxidase and the production of ROS trigger TRAF6 auto-ubiquitination, which recruits TAB2 and promotes the formation of a TAK1 activation complex, directly enhancing the binding of TRAF6 to TAK1, leading to the TAK1 ubiquitination.
What does TRAF6 stand for?
TNF receptor-associated factor 6 (TRAF6) is a RING-type ubiquitin ligase that promotes polyubiquitination required for the signaling of many innate immune receptors.
What is the function of ubiquitination?
Ubiquitination affects cellular process by regulating the degradation of proteins (via the proteasome and lysosome), coordinating the cellular localization of proteins, activating and inactivating proteins, and modulating protein-protein interactions.
Why is ubiquitin important?
Ubiquitin plays an important role in regulating protein on the cellular level. Doctors believe it has promising potential for a variety of targeted cellular medicine treatments. The study of ubiquitin has already led to the development of medications for the treatment of multiple myeloma, a form of blood cancer.
How is TRAF6 activated?
TRAF6-dependent activation of danger signals (signal 1: such as TLR pathways) induces the production of psoriasis mediator from keratinocytes. Subsequent activation of the IL-23/IL-17 axis in DC–T cell interaction gives rise to the production of IL-17 (signal 2) that drives further activation of keratinocytes.
What is Irak immunology?
Interleukin-1 receptor-associated kinases (IRAK) play a central role in inflammatory responses by regulating the expression of various inflammatory genes in immune cells. These signals are critical for elimination of viruses, bacteria, and cancer cells, as well as for wound healing.
What is the mechanism of action of TRAF6?
TRAF6 targets cGAS for poly-ubiquitination. TRAF6 activates cGAS-STING signaling. TRAF6 enhances anti-DNA virus innate immunity.
How does TRAF6 activate cGAS-STING signaling?
TRAF6 activates cGAS-STING signaling. TRAF6 enhances anti-DNA virus innate immunity. cGAS-STING (stimulator of interferon genes) signaling is crucial for the recognition of cytoplasmic double-stranded DNA by host cells and consequently activating innate immune response by promoting the production cGAMP and type I interferon.
Is TRAF6 a potential drug target in tumor immunity?
Therefore, TRAF6-induced polyubiquitination of cGAS is probably required for cytosolic DNA sensing and subsequent anti-viral immunity. Given that cGAS is also important in recognition of the DNAs released by tumor cells [ 28, 29 ], we propose TRAF6 as a novel regulator and potential drug target in tumor immunity.
Is TRAF6 a regulator of CGAS mediated anti-viral innate immunity?
In this study, we identified TRAF6 as a regulator of cGAS mediated anti-viral innate immunity. Our data showed that either ectopic expression or knockdown of TRAF6 modulates the double strand DNA induced expression of interferon-responsive genes. Mechanistically, TRAF6 specifically promotes cGAS activation by targeting cGAS for ubiquitination.
