A novel mechanism of control of NFκB activation and inflammation involving A2B adenosine receptors.
نویسندگان
چکیده
The nuclear factor kappa B (NFκB) pathway controls a variety of processes, including inflammation, and thus, the regulation of NFκB has been a continued focus of study. Here, we report a newly identified regulation of this pathway, involving direct binding of the transcription factor NFκB1 (the p105 subunit of NFκB) to the C-terminus of the A(2B) adenosine receptor (A(2B)AR), independent of ligand activation. Intriguingly, binding of A(2B)AR to specific sites on p105 prevents polyubiquitylation and degradation of p105 protein. Ectopic expression of the A(2B)AR increases p105 levels and inhibits NFκB activation, whereas p105 protein levels are reduced in cells from A(2B)AR-knockout mice. In accordance with the known regulation of expression of anti- and pro-inflammatory cytokines by p105, A(2B)AR-null mice generate less interleukin (IL)-10, and more IL-12 and tumor necrosis factor (TNF-α). Taken together, our results show that the A(2B)AR inhibits NFκB activation by physically interacting with p105, thereby blocking its polyubiquitylation and degradation. Our findings unveil a surprising function for the A(2B)AR, and provide a novel mechanistic insight into the control of the NFκB pathway and inflammation.
منابع مشابه
A novel mechanism of control of NFkB activation and inflammation involving A2B adenosine receptors
o u rn a l o f C e ll S c ie n c e A novel mechanism of control of NFkB activation and inflammation involving A2B adenosine receptors Ying Sun, Yuanyuan Duan, Anna S. Eisenstein, Wenbao Hu, Adrien Quintana, Wai Kwan Lam, Yan Wang, Zhenguo Wu, Katya Ravid and Pingbo Huang* Division of Life Science, and State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology...
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ورودعنوان ژورنال:
- Journal of cell science
دوره 125 Pt 19 شماره
صفحات -
تاریخ انتشار 2012