期刊
GENES & DEVELOPMENT
卷 22, 期 15, 页码 2093-2101出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1680708
关键词
NF-kappa B signaling; negative feedback; computational modeling; temporal control; I kappa B alpha; A20
资金
- NIGMS NIH HHS [R01 GM072024, R01 GM72024, R01 GM071573, R01 GM071573-04] Funding Source: Medline
TNF-induced NF-kappa B activity shows complex temporal regulation whose different phases lead to distinct gene expression programs. Combining experimental studies and mathematical modeling, we identify two temporal amplification steps -one determined by the obligate negative feedback regulator I kappa B alpha-that define the duration of the first phase of NF-kappa B activity. The second phase is defined by A20, whose inducible expression provides for a rheostat function by which other inflammatory stimuli can regulate TNF responses. Our results delineate the nonredundant functions implied by the knockout phenotypes of i kappa b alpha and a20, and identify the latter as a signaling cross-talk mediator controlling inflammatory and developmental responses.
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