DIFFERENTIAL REGULATION OF THE C-MYC ONCOGENE PROMOTER BY THE NF-KAPPA-B REL FAMILY OF TRANSCRIPTION FACTORS
DIFFERENTIAL REGULATION OF THE C-MYC ONCOGENE PROMOTER BY THE NF-KAPPA-B REL FAMILY OF TRANSCRIPTION FACTORS
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DOI：
10.1128/mcb.14.2.1039
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发表时间：
1994-02-01
影响因子：
5.3
通讯作者：
SONENSHEIN, GE
中科院分区：
文献类型：
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作者：
LAROSA, FA;PIERCE, JW;SONENSHEIN, GE
小鼠 c-myc 基因包含两个对 NF-κ B 因子相关癌基因家族有反应的元件。之前我们已经证明，在白细胞介素-1处理人真皮成纤维细胞和T细胞中人T细胞白血病病毒I型tax基因表达时，与这两个NF-κB元件结合的因子介导c-myc启动子转录的诱导（D. J. Kessler、M. P. Duyao、D. B. Spicer和G. E. Sonenshein，J Exp. Med. 176：787-792，1992；M.P.Duyao、D.J.Kessler、D.B.Spicer、C.Bartholomew、J.L.Cleveland、M.Siekevitz 和 G.E.Sonenshein，J.Chem.267：16288-16291。为了开始描述 NF-kappa B 家族各个成员的具体作用，我们在这里测试了它们对 NIH 3T3 细胞中 c-myc 启动子/外显子 1-CAT 构建体激活的影响。经典 NF-kappa B (p65/p50) 是 c-myc 启动子的有效转录激活剂。单独使用 p65 或 p65 与 p50 组合进行共转染可介导显着的诱导作用。相反，v-rel 或鸡 c-rel 的表达均未能反式激活，而鼠 c-rel 仅轻微诱导 c-myc 启动子活性。此外，经典 NF-κ B 的诱导受到 v-rel 或鸡 c-rel 共表达的抑制。因此，rel 家族的各个成员对 c-myc 启动子具有不同的影响，c-myc 启动子可以调节整体转录活性，并允许在不同的生理条件下精确调节该癌基因。
The murine c-myc gene contains two elements responsive to the rel-oncogene-related family of NF-kappa B factors. Previously we have shown that factor binding to these two NF-kappa B elements mediates induction of transcription of the c-myc promoter upon interleukin-l treatment of human dermal fibroblasts and human T cell leukemia virus type I tax gene expression in T cells (D. J. Kessler, M. P. Duyao, D. B. Spicer, and G. E. Sonenshein, J Exp. Med. 176:787-792, 1992; M. P. Duyao, D. J. Kessler, D. B. Spicer, C. Bartholomew, J. L. Cleveland, M. Siekevitz, and G. E. Sonenshein, J. Biol. Chem. 267:16288-16291, 1992). To begin to delineate the specific roles of the individual members of the NF-kappa B family, here we have tested their effects on activation of a c-myc promoter/exon 1-CAT construct in NIH 3T3 cells. Classical NF-kappa B (p65/p50) was a potent transcriptional activator of the c-myc promoter. Cotransfection with either p65 alone or p65 in combination with p50 mediated significant induction. In contrast, expression of either v-rel or chicken c-rel failed to transactivate, while murine c-rel induced c-myc promoter activity only slightly. Furthermore, induction by classical NF-kappa B was inhibited by coexpression of either v-rel or chicken c-rel. Thus, individual members of the rel family have differential effects on the c-myc promoter, which can modulate overall transcriptional activity and allow for precise regulation of this oncogene under diverse physiologic conditions.