Ten R M, Paya C V, Israël N, Le Bail O, Mattei M G, Virelizier J L, Kourilsky P, Israël A
Unité de Biologie Moléculaire du Gène, Institut Pasteur, Paris, France.
EMBO J. 1992 Jan;11(1):195-203. doi: 10.1002/j.1460-2075.1992.tb05042.x.
In order to characterize the regulation of the gene encoding the p50 subunit of the transcription factor NF-kappa B, we have isolated a human genomic clone, and sequenced the promoter of this gene. By in situ hybridization we have mapped the gene encoding the p50 subunit of NF-kappa B to the 4q23-4q25 region of the human genome and the H1-H3 region of the murine chromosome 3. The p50 promoter lacks TATA and CAAT elements, but contains NF-kappa B, AP-1 and HIP-1 binding sequence. The kappa B motif binds NF-kappa B, KBF1, and heterodimers of p50 and c-rel, suggesting that the gene is regulated by members of this family. Co-transfection experiments demonstrate that the p50 promoter can be activated by either of the two subunits of NF-kappa B (p50 and p65), and more strongly by the combination of both. The promoter of p50 can be activated by phorbol esters and tumor necrosis factor alpha but not by forskolin and these responses are mediated through the NF-kappa B binding sequence. The involvement of NF-kappa B in the regulation of the p50 gene is also supported by the inhibition of the PMA activation of the promoter by an NF-kappa B transdominant negative mutant, as well as the product of the v-rel oncogene.
为了阐明转录因子NF-κB的p50亚基编码基因的调控机制，我们分离了一个人类基因组克隆，并对该基因的启动子进行了测序。通过原位杂交，我们将NF-κB的p50亚基编码基因定位到人类基因组的4q23-4q25区域以及小鼠染色体3的H1-H3区域。p50启动子缺乏TATA和CAAT元件，但含有NF-κB、AP-1和HIP-1结合序列。κB基序可结合NF-κB、KBF1以及p50和c-rel的异二聚体，这表明该基因受该家族成员的调控。共转染实验表明，p50启动子可被NF-κB的两个亚基（p50和p65）中的任何一个激活，二者共同作用时激活作用更强。p50启动子可被佛波酯和肿瘤坏死因子α激活，但不能被福斯高林激活，这些反应是通过NF-κB结合序列介导的。NF-κB的反式显性负突变体以及v-rel癌基因产物对启动子的PMA激活的抑制作用也支持了NF-κB参与p50基因的调控。
