Autoregulatory feedback loops terminating the NF-kappa B response

After nuclear factor (NF)-kappa B activation, a complex network of negative feedback loops ensures that the termination of the NF-kappa B; response occurs in a highly organized manner. Recent results show that signals initiated during the induction phase already program a default termination procedure that enables temporally and spatially regulated NF-kappa B deactivation. All negative feedback mechanisms occur with a characteristic time delay, thereby permitting full NF-kappa B function during the interim period. Some proteins that direct termination are produced directly in response to NF-kappa B activation, whereas others are activated via inducible binding or by protein stabilization. Another time-delaying strategy of NF-kappa B feedback inhibitory proteins relies on their ability to function as timers and molecular clockworks with the intrinsic property to terminate their own activity within a preset period.