期刊
CELL SYSTEMS
卷 5, 期 6, 页码 549-+出版社
CELL PRESS
DOI: 10.1016/j.cels.2017.10.019
关键词
-
资金
- American Cancer Society [IRG-95-125-13]
- National Institute of General Medical Sciences [1R01GM115650]
- Department of Defense Neurofibromatosis Research Program [W81XWH-16-1-0085]
- American Association for Cancer Research Stand Up To Cancer [SU2C-AACR-IRG-01-16]
- American Association for Cancer Research
- scientific partner of SU2C
- UC Davis Comprehensive Cancer Center Support Grant (CCSG) - National Cancer Institute [NCI P30CA093373]
ERK signaling regulates the expression of target genes, but it is unclear how ERK activity dynamics are interpreted. Here, we investigate this question using simultaneous, live, single-cell imaging of two ERK activity reporters and expression of Fra-1, a target gene controlling epithelial cell identity. We find that Fra-1 is expressed in proportion to the amplitude and duration of ERK activity. In contrast to previous persistence detector'' and selective filter'' models in which Fra-1 expression only occurs when ERK activity persists beyond a threshold duration, our observations demonstrate that the network regulating Fra-1 expression integrates total ERK activity and responds to it linearly. However, exploration of a generalized mathematicalmodel of the Fra-1 coherent feedforward loop demonstrates that it can perform either linear integration or persistence detection, depending on the basal mRNA production rate and protein production delays. Our data indicate that significant basal expression and short delays cause Fra-1 to respond linearly to integrated ERK activity.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据