The F-box protein Fbl10 is a novel transcriptional repressor of c-Jun
The F-box protein Fbl10 is a novel transcriptional repressor of c-Jun
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DOI：
10.1038/ncb1628
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发表时间：
2007-09-01
影响因子：
21.3
通讯作者：
Tanese, Naoko
中科院分区：
文献类型：
--
作者：
Koyama-Nasu, Ryo;David, Gregory;Tanese, Naoko
c-Jun是异源二聚体转录因子AP-1的一种成分，可在紫外线（UV）下迅速激活（1）。在未应激的细胞中，c-Jun活性受转录阻遏物复合物负调控。在这里，我们表明，F-box蛋白Fbl 10/JHDM 1B与c-Jun相互作用，抑制c-Jun介导的转录。染色质免疫沉淀试验表明，Fbl 10是目前在c-Jun启动子，和c-Jun是必需的Fbl 10的招聘。Fbl 10通过CxxC锌指和系链转录抑制因子复合物与c-jun启动子中未甲基化的CpG序列结合。通过RNA干扰（RNAi）抑制Fbl 10表达可诱导c-jun和其他c-Jun靶基因的转录，并导致异常的细胞周期进程和增加的UV诱导的细胞死亡。此外，Fbl 10蛋白和信使RNA下调响应于UV与c-Jun的负相关。综上所述，我们的结果表明，Fbl 10是c-Jun功能的关键调节器。
c-Jun is a component of the heterodimeric transcription factor AP-1 that is rapidly activated in response to ultraviolet light (UV)(1). In unstressed cells, c-Jun activity is negatively regulated by transcriptional repressor complexes. Here we show that the F-box protein Fbl10/JHDM1B interacts with c-Jun and represses c-Jun-mediated transcription. Chromatin-immunoprecipitation assays demonstrate that Fbl10 is present at the c-jun promoter, and that c-Jun is required for the recruitment of Fbl10. Fbl10 binds to the unmethylated CpG sequences in the c-jun promoter through the CxxC zinc finger and tethers transcriptional repressor complexes. Suppression of Fbl10 expression by RNA interference (RNAi) induces transcription of c-jun and other c-Jun-target genes, and causes an aberrant cell-cycle progression and increased UV-induced cell death. Furthermore, Fbl10 protein and messenger RNA are downregulated in response to UV in an inverse correlation with c-Jun. Taken together, our results demonstrate that Fbl10 is a key regulator of c-Jun function.