Oscillations in NFkB signaling pathway

Yunjiao Wang
MBI - Postdoc, The Ohio State University

(November 19, 2009 10:30 AM - 11:18 AM)

Oscillations in NFkB signaling pathway

Abstract

The transcription factor NF-kB is critical to the control of responses to cellular stress, inter- and intracellular signaling, cell growth, survival and apoptosis. At rest, NF-kB is sequestered by its inhibitor IkB in the cytoplasm. Upon stimulation, such as tumor necrosis factor $alpha$ (TNF$alpha$), NF-kB gets released from IkB and translocates to the nucleus and regulates genes transcription, including regulating transcription of gene IkB. Then the newly synthesized IkB, on the other hand, removes NF-kB from the nucleus. Hence, NF-kB and IkB form a negative feedback loop. Negative feedback loop is often associated to oscillations. Indeed, oscillations of the concentration of nuclear NF-kB has been observed both at population and single cell levels by Hoffmann et al. and Nelson et al. respectively. Ashall et al. recently reported that different frequencies of the oscillations leads to different gene expression. It has been reported in many works that NF-kB signaling pathway may interact with many other signaling pathways, including P53 signaling pathway. So it is important to understand that how the frequencies of NF-kB oscillations may be influenced by its interacting signals. However, the existence and mechanism of those potential interactions are not clear. In this talk, I study this issue by considering the pathway subjected to two types of putative signals: sinusoid and pulsate signals. A rich variety of nonlinear dynamics can be observed. In addition, we consider possible cell-cell communication by secretion of TNF$alpha$.