Autoregulatory feedback loops terminating the NF-kappaB response.

After nuclear factor (NF)-kappaB activation, a complex network of negative feedback loops ensures that the termination of the NF-kappaB 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-kappaB deactivation. All negative feedback mechanisms occur with a characteristic time delay, thereby permitting full NF-kappaB function during the interim period. Some proteins that direct termination are produced directly in response to NF-kappaB activation, whereas others are activated via inducible binding or by protein stabilization. Another time-delaying strategy of NF-kappaB 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.