Saccani Simona, Pantano Serafino, Natoli Gioacchino
Institute for Research in Biomedicine, Via Vela 6, CH6500 Bellinzona, Switzerland.
Mol Cell. 2003 Jun;11(6):1563-74. doi: 10.1016/s1097-2765(03)00227-2.
Transcription factors within a family usually share the ability to recognize similar or identical consensus sites. For example, the five mammalian NF-kappaB/Rel proteins generate more than 12 dimers recognizing 9-11 nucleotide kappaB sites. Each dimer selectively regulates a few target promoters; however, several genes are redundantly induced by more than one dimer. Whether this property simply generates redundancy in target gene activation or underlies more complex regulatory mechanisms is an open issue. We show here that during dendritic cell maturation, rapidly activated dimers (e.g., p50/RelA) bound to a subset of target promoters are gradually replaced by slowly activated dimers (e.g., p52/RelB). Since the dimers have different transcriptional activity at each promoter, the dimer exchange allows fine tuning of the response over time. Further, due to the insensitivity of p52/RelB to the NF-kappaB inhibitors, the IkappaBs, dimer exchange contributes to sustained activation of selected NF-kappaB targets in spite of the resynthesis of IkappaBalpha.
同一家族内的转录因子通常具有识别相似或相同共有序列的能力。例如，五种哺乳动物的NF-κB/Rel蛋白可形成超过12种二聚体，识别9至11个核苷酸的κB位点。每个二聚体选择性地调控少数几个靶启动子；然而，有几个基因可被不止一种二聚体冗余诱导。这种特性仅仅是在靶基因激活中产生冗余，还是更复杂调控机制的基础，这仍是一个悬而未决的问题。我们在此表明，在树突状细胞成熟过程中，与一部分靶启动子结合的快速激活二聚体（如p50/RelA）会逐渐被缓慢激活的二聚体（如p52/RelB）取代。由于二聚体在每个启动子处具有不同的转录活性，二聚体交换使得反应能够随时间进行微调。此外，由于p52/RelB对NF-κB抑制剂IkappaB不敏感，尽管IkappaBα重新合成，但二聚体交换仍有助于所选NF-κB靶标的持续激活。
