INDEPENDENT MODES OF TRANSCRIPTIONAL ACTIVATION BY THE P50-SUBUNIT AND P65-SUBUNIT OF NF-KAPPA-B
INDEPENDENT MODES OF TRANSCRIPTIONAL ACTIVATION BY THE P50-SUBUNIT AND P65-SUBUNIT OF NF-KAPPA-B
复制标题
DOI：
10.1101/gad.6.5.775
复制
发表时间：
1992-05-01
影响因子：
10.5
通讯作者：
BALTIMORE, D
中科院分区：
文献类型：
--
作者：
FUJITA, T;NOLAN, GP;BALTIMORE, D
分析转录因子NF-κ-B的重组亚基p50和p65与各种κ-B基序的结合和体外活化。亚基优先形成激活转录的异源二聚体。尽管p50和p65作为同源二聚体单独结合DNA并且在结构上相关，但它们的激活机制是不同的。p65通过其独特的羧基末端激活结构域激活转录。对于许多不同的kappa-B基序，（p50）2显示出比（p65）更高的DNA结合亲和力，并且仅当采用由某些kappa-B基序而不是其他基序诱导的胰凝乳蛋白酶抗性构象时才提供强的转录激活。因此，（p50）2作为一个积极的调节剂在体外，其分离作为一个假定的组成型调节MHC I类基因一致。因此，NF-κ-B的两个亚基独立地对给定的κ-B基序提供调节。
Recombinant subunits of the transcription factor NF-kappa-B, p50 and p65, were analyzed both for binding to various kappa-B motifs and in vitro activation. The subunits preferentially form a heterodimer that activates transcription. Although p50 and p65 bind DNA individually as homodimers and are structurally related, their activation mechanisms are distinct. p65 activates transcription by its unique carboxy-terminal activation domain. (p50)2 displays higher affinity DNA binding than (p65), for many distinct kappa-B motifs and provides strong transcriptional activation only when adopting a chymotrypsin-resistant conformation induced by certain kappa-B motifs but not others. Thus, (p50)2 acts as a positive regulator in vitro, consistent with its isolation as a putative constitutive regulator of MHC class I genes. Both subunits of NF-kappa-B, therefore, contribute independently to provide regulation at given kappa-B motifs.