IkappaBepsilon provides negative feedback to control NF-kappaB oscillations, signaling dynamics, and inflammatory gene expression.

ABSTRACT: NF-kappaB signaling is known to be critically regulated by the NF-kappaB-inducible inhibitor protein IkappaBalpha. The resulting negative feedback has been shown to produce a propensity for oscillations in NF-kappaB activity. We report integrated experimental and computational studies that demonstrate that another IkappaB isoform, IkappaBepsilon, also provides negative feedback on NF-kappaB activity, but with distinct functional consequences. Upon stimulation, NF-kappaB-induced transcription of IkappaBepsilon is delayed, relative to that of IkappaBalpha, rendering the two negative feedback loops to be in antiphase. As a result, IkappaBepsilon has a role in dampening IkappaBalpha-mediated oscillations during long-lasting NF-kappaB activity. Furthermore, we demonstrate the requirement of bot

SUBMITTER: Kearns JD 

PROVIDER: S-EPMC2063883 | biostudies-literature | 2006 Jun

REPOSITORIES: biostudies-literature