Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: Modeling time delay in the NF B signaling pathway following low dose IL-1 stimulation | Witt et al. EURASIP Journal on Bioinformatics and Systems Biology 2011 2011 3 http content 2011 1 3 s EURASIP Journal on Bioinformatics and Systems Biology a SpringerOpen Journal RESEARCH Open Access Modeling time delay in the NF fB signaling pathway following low dose IL-1 stimulation 1 2 1 1 2 13 Johannes Witt Sandra Barisic Oliver Sawodny Michael Ederer Dagmar Kulms and Thomas Sauter Abstract Stimulation of human epithelial cells with IL-1 10 ng ml UVB radiation results in sustained NFkB activation caused by continuous IKKp phosphorylation. We have recently published a strictly reduced ordinary differential equation model elucidating the involved mechanisms. Here we compare model extensions for low IL-1 doses ng ml where delayed IKKp phosphorylation is observed. The extended model including a positive regulatory element most likely auto-ubiquitination of TRAF6 reproduces the observed experimental data most convincingly. The extension is shown to be consistent with the original model and contains very sensitive processes which may serve as potential intervention targets. Keywords IKKbeta TRAF6 mathematical model IL-1 UVB Introduction The transcription factor NFkB is of central importance in inflammation and anti-apoptotic signaling. Upon stimulation of human epithelial cells with IL-1 NFkB becomes activated due to proteasomal degradation of its cellular inhibitor . This process requires phosphorylation of by the upstream kinase IKKp. Since sustained expression of anti-apoptotic genes contributes to the maintenance of a range of cancers its activity is tightly regulated and terminated by a negative feedback loop as NFkB promotes . synthesis. Accordingly various approaches to anti-cancer strategies involve inhibition of the NFkB signaling pathway 1 . Interestingly NFkB is converted into a pro-apoptotic factor upon stimulation with IL-1 UVB. The persistence of this effect is ensured by sustained NFkB .
