INTERACTION OF AN NF-KAPPA-B-LIKE FACTOR WITH A SITE UPSTREAM OF THE C-MYC PROMOTER
INTERACTION OF AN NF-KAPPA-B-LIKE FACTOR WITH A SITE UPSTREAM OF THE C-MYC PROMOTER
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DOI：
10.1073/pnas.87.12.4727
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发表时间：
1990-06-01
影响因子：
11.1
通讯作者：
SONENSHEIN, GE
中科院分区：
文献类型：
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作者：
DUYAO, MP;BUCKLER, AJ;SONENSHEIN, GE
c-myc原癌基因与哺乳动物细胞的生长和分化控制有关。例如，生长停滞通常在c-myc mRNA和基因转录减少之前。为了阐明控制c-myc基因转录的机制，我们已经开始表征核因子与位于小鼠基因P1起始位点上游1139-421 bp的719碱基对（bp）c-myc调控结构域的相互作用。从指数生长的WEHI 231小鼠B淋巴瘤细胞的核提取物在迁移率变化测定中形成多个复合物。在生长停滞的WEHI 231细胞中观察到复合物分布的变化，并且这种相互作用的主要位点定位于与NF-κ B家族蛋白识别的序列相似的21-bp序列。通过寡核苷酸竞争证明NF-κ B样因子的结合。在70 Z/3前B-至B-细胞分化时复合物形成的诱导、GTP结合的增强和去污剂诱导的抑制蛋白的释放表明NF-κ B本身是可以结合的家族的一个成员。含有21-bp c-myc序列的胸苷激酶-氯霉素乙酰转移酶构建体转染到Jurkat细胞中，表明佛波酯和植物血凝素处理后氯霉素乙酰转移酶活性增加。这些结果表明NF-κ B样因子参与了c-myc转录的调节。
The c-myc protooncogene has been implicated in control of growth and differentiation of mammalian cells. For instance, growth arrest is often preceded by reduction in c-myc mRNA and gene transcription. To elucidate the mechanisms of control of c-myc gene transcription, we have begun to characterize the interaction of nuclear factors with the 719-base-pair (bp) c-myc regulatory domain, located 1139-421 bp upstream of the P1 start site of the mouse gene. Nuclear extracts from exponentially growing WEHI 231 murine B-lymphoma cells formed multiple complexes in mobility-shift assays. Changes in complex distribution were observed in growth-arrested WEHI 231 cells, and a major site of this interaction mapped to a 21-bp sequence that is similar to the sequences recognized by the NF-.kappa.B family of proteins. Binding of NF-.kappa.B-like factors was demonstrated by oligonucleotide competition. Induction of complex formation upon 70Z/3 pre-B- to B-cell differentiation, enhancement of binding by GTP, and detergent-induced release of inhibitor protein suggested that NF-.kappa.B itself is one member of the family that can bind. Transfection of thymidine kinase-chloramphenicol acetyltransferase constructs containing the 21-bp c-myc sequence into Jurkat cells demonstrated increased chloramphenicol acetyltransferase activity upon phorbol ester and phytohemagglutinin treatment. These results suggest the involvement of NF-.kappa.B-like factors in the regulation of c-myc transcription.