Biomedical Center, School of Electronic Engineering, Beijing University of Posts and Telecommunications, Beijing, China.
Cell Biochem Funct. 2012 Oct;30(7):582-7. doi: 10.1002/cbf.2837. Epub 2012 Jun 6.
We constructed the significant low-expression P-glycoprotein (ABCB1) inhibited transport and signal network in chimpanzee compared with high-expression (fold change ≥2) the human left cerebrum in GEO data set, by using integration of gene regulatory activated and inhibited network inference method with gene ontology (GO) analysis. Our result showed that ABCB1 transport and signal upstream network RAB2A inhibited ABCB1, and downstream ABCB1-inhibited SMAD1_2, NCK2, SLC25A46, GDF10, RASGRP1, EGFR, LRPPRC, RASSF2, RASA4, CA2, CBLB, UBR5, SLC25A16, ITGB3BP, DDIT4, PDPN, RAB2A in chimpanzee left cerebrum. We obtained that the different biological processes of ABCB1 inhibited transport and signal network repressed carbon dioxide transport, ER to Golgi vesicle-mediated transport, folic acid transport, mitochondrion transport along microtubule, water transport, BMP signaling pathway, Ras protein signal transduction, transforming growth factor beta receptor signaling pathway in chimpanzee compared with the inhibited network of the human left cerebrum, as a result of inducing inhibition of mitochondrion transport along microtubule and BMP signal-induced cell shape in chimpanzee left cerebrum. Our hypothesis was verified by the same and different biological processes of ABCB1 inhibited transport and signal network of chimpanzee compared with the corresponding activated network of chimpanzee and the human left cerebrum, respectively.
我们构建了一个显著低表达 P-糖蛋白（ABCB1）的转运和信号网络，该网络在人类左大脑中高表达（fold change≥2），方法是整合基因调控激活和抑制网络推断方法与基因本体（GO）分析。我们的结果表明，ABCB1 转运和信号的上游网络 RAB2A 抑制了 ABCB1，下游的 ABCB1 抑制了 SMAD1_2、NCK2、SLC25A46、GDF10、RASGRP1、EGFR、LRPPRC、RASSF2、RASA4、CA2、CBLB、UBR5、SLC25A16、ITGB3BP、DDIT4、PDPN、RAB2A 在黑猩猩左大脑中。我们发现，ABCB1 抑制转运和信号网络的不同生物学过程抑制了二氧化碳转运、内质网到高尔基体囊泡介导的转运、叶酸转运、线粒体沿微管的转运、水转运、BMP 信号通路、Ras 蛋白信号转导、转化生长因子β受体信号通路，在黑猩猩中，与人类左大脑中的抑制网络相比，这导致了线粒体沿微管的转运和 BMP 信号诱导的细胞形状抑制。我们的假设通过比较黑猩猩和人类左大脑的相同和不同生物学过程的 ABCB1 抑制转运和信号网络得到了验证。
