Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01, Centros, Singapore 138668, Singapore.
Comput Biol Med. 2011 Jul;41(7):512-28. doi: 10.1016/j.compbiomed.2011.04.017. Epub 2011 May 31.
TNFα-mediated apoptosis is one of the complex and tightly regulated cellular processes as it involves the activation of both pro- and anti-apoptotic signaling pathways. Thus, it is important to elucidate the molecular players of this process and their dynamics in order to gain an in-depth understanding of the mechanisms underlying apoptosis. To this end, we proposed an integrated model of TNFα-mediated apoptosis pathway in Type I cells, formulated based on the principles of mass action kinetics. The model includes major apoptotic modules-the extrinsic and intrinsic pathways, the NFκB survival signaling and various regulatory mechanisms. We performed simulations and sensitivity analyses to study the role of NFκB pathway in regulating apoptosis, and identified IAP as one of the more potent regulators of apoptosis.
TNFα 介导体细胞凋亡是一个复杂且受到严格调控的细胞过程，因为它涉及到促凋亡和抗凋亡信号通路的激活。因此，阐明这个过程的分子参与者及其动力学对于深入了解细胞凋亡的机制非常重要。为此，我们基于质量作用动力学原理，提出了一种在 I 型细胞中 TNFα 介导体细胞凋亡途径的综合模型。该模型包括主要的凋亡模块——外在途径和内在途径、NFκB 存活信号和各种调节机制。我们进行了模拟和敏感性分析，以研究 NFκB 通路在调节细胞凋亡中的作用，并确定 IAP 是凋亡的更有力调节因子之一。
