Oscillation dynamics underlie functional switching of NF-κB for B-cell activation

2016年10月20日 npj Systems Biology and Applications 2, Article number:16024 (2016) doi:10.1038/npjsba.2016.24




B cells: Two feedback loops control gene regulator
Different feedback loops impact the dynamics of the transcription factor NF-κB in the development of B-cells of the immune system. A team led by Mariko Okada-Hatakeyama from RIKEN and Osaka University, Japan, constructed a mathematical model of B-cell receptor signaling with expression dynamics of NF-κB, a protein complex that regulates multiple genes involved in controlling cell fate. The researchers also conducted lab experiments with B-cells with modified NF-κB networks to test and validate their model. They showed that NF-κB is activated in a switch-like manner by positive feedback regulation of an upstream modulator called IKK. NF-κB levels then oscillate by negative feedback regulation to induce target genes. The findings show how different, independent feedback loops can operate together to control regulatory pathways involved in B cell differentiation.


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