Waterfield Michael R, Zhang Minying, Norman Lourdes P, Sun Shao Cong
Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Mol Cell. 2003 Mar;11(3):685-94. doi: 10.1016/s1097-2765(03)00070-4.
NF-kappaB family of transcription factors plays a pivotal role in regulation of immune and inflammatory responses. NF-kappaB is known to function by binding to the kappaB enhancer and directly activating target gene transcription. Here we demonstrate another function of NF-kappaB, in which the nfkappab1 gene product p105 regulates MAP kinase signaling triggered by the bacterial component lipopolysaccharide. p105 exerts this signaling function by controlling the stability and function of an upstream kinase, Tpl2. In macrophages, Tpl2 forms a stable and inactive complex with p105, and activation of Tpl2 involves its dissociation from p105 and subsequent degradation. Thus, p105 functions as a physiological partner and inhibitor of Tpl2, which provides an example of how a transcription factor component regulates upstream signaling events.
转录因子NF-κB家族在免疫和炎症反应的调节中起关键作用。已知NF-κB通过与κB增强子结合并直接激活靶基因转录来发挥功能。在此，我们证明了NF-κB的另一种功能，其中nfkappab1基因产物p105调节由细菌成分脂多糖触发的丝裂原活化蛋白激酶信号传导。p105通过控制上游激酶Tpl2的稳定性和功能来发挥这种信号传导功能。在巨噬细胞中，Tpl2与p105形成稳定且无活性的复合物，Tpl2的激活涉及它与p105的解离及随后的降解。因此，p105作为Tpl2的生理伴侣和抑制剂发挥作用，这提供了一个转录因子成分如何调节上游信号事件的例子。
