A homeostatic model of IkappaB metabolism to control constitutive NF-kappaB activity.
A homeostatic model of IkappaB metabolism to control constitutive NF-kappaB activity.
复制标题
IKAPPAB代谢的一种稳态模型，以控制构成型NF-kappab活动。
DOI：
10.1038/msb4100148
复制
发表时间：
2007
影响因子：
9.9
通讯作者：
Hoffmann, Alexander
中科院分区：
文献类型：
--
作者：
O'Dea, Ellen L.;Barken, Derren;Peralta, Raechel Q.;Tran, Kim T.;Werner, Shannon L.;Kearns, Jeffrey D.;Levchenko, Andre;Hoffmann, Alexander
Cellular signal transduction pathways are usually studied following administration of an external stimulus. However, disease-associated aberrant activity of the pathway is often due to misregulation of the equilibrium state. The transcription factor NF-κB is typically described as being held inactive in the cytoplasm by binding its inhibitor, IκB, until an external stimulus triggers IκB degradation through an IκB kinase-dependent degradation pathway. Combining genetic, biochemical, and computational tools, we investigate steady-state regulation of the NF-κB signaling module and its impact on stimulus responsiveness. We present newly measured in vivo degradation rate constants for NF-κB-bound and -unbound IκB proteins that are critical for accurate computational predictions of steady-state IκB protein levels and basal NF-κB activity. Simulations reveal a homeostatic NF-κB signaling module in which differential degradation rates of free and bound pools of IκB represent a novel cross-regulation mechanism that imparts functional robustness to the signaling module.
登录
查看更多内容
影响因子：
56.9
作者：
Jaakkola, P;Mole, DR;Ratcliffe, PJ
通讯作者：
Ratcliffe, PJ
影响因子：
56.9
作者：
Ivan, M;Kondo, K;Kaelin, WG
通讯作者：
Kaelin, WG
影响因子：
56.9
作者：
Hoffmann, A;Levchenko, A;Baltimore, D
通讯作者：
Baltimore, D
影响因子：
7.8
作者：
Kearns, Jeffrey D.;Basak, Soumen;Hoffmann, Alexander
通讯作者：
Hoffmann, Alexander
影响因子：
11.4
作者：
Krappmann, D;Wulczyn, FG;Scheidereit, C
通讯作者：
Scheidereit, C