hnulp1, a basic helix-loop-helix protein with a novel transcriptional repressive domain, inhibits transcriptional activity of serum response factor

hnulp1, a basic helix-loop-helix protein with a novel transcriptional repressive domain, inhibits transcriptional activity of serum response factor
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hnulp1 是一种具有新型转录抑制结构域的碱性螺旋-环-螺旋蛋白,可抑制血清反应因子的转录活性

DOI:
10.1016/j.bbrc.2006.02.187
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发表时间:
2006-05-12
影响因子:
3.1
通讯作者:
Wu, XS
Wu, XS
中科院分区:
生物学4区
文献类型:
--
作者:
Cai, ZY;Wang, YQ;Wu, XS

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许多bHLH蛋白参与心脏发育和心血管疾病。在此,我们鉴定并表征了小鼠基因nulp1的人类同源物(hnulp1)。预测的蛋白在n端和c端分别含有bHLH结构域和DUF654结构域。Northern blot分析显示,一个2.3 kb的转录本在早期人类胚胎和成人组织中广泛表达,尤其是在成人心脏中表达水平更高。当融合到GAL4 dna结合域并与VP-16共转染时,hnulp1是一个转录抑制因子,其中DUF654基序代表基本的转录抑制活性。用trichostatin A处理细胞可以缓解这种抑制,这表明DUF654基序通过增加gal4驱动启动子上的去乙酰化酶活性起作用。COS-7细胞中过表达hnulp1蛋白可抑制血清反应因子(SRF)的转录活性,提示hnulp1可能作为SRF信号通路中bHLH的新型转录抑制因子介导细胞功能。(c) 2006爱思唯尔公司版权所有。
Many bHLH proteins are involved in cardiac development and cardiovascular diseases. Herein, we identified and characterized the human homologue (hnulp1) of mouse gene nulp1. The predicted protein contains a bHLH domain and a DUF654 domain in N-terminal and C-terminal, respectively. Northern blot analysis shows that a 2.3-kb transcript expressed broadly in early human embryonic and adult tissues, especially with a higher level in adult heart. hnulp1 is a transcription repressor when fused to GAL4 DNA-binding domain and co-transfected with VP-16, in which DUF654 motif represents the basal transcriptional repressive activity. Treatment of cells with trichostatin A can relieve this repression, suggesting that the DUF654 motif acts through increasing deacetylase activity at the GAL4-driven promoter. Overexpression of hnulp1 protein in COS-7 cells inhibits the transcriptional activity of serum response factor (SRF), suggesting that hnulp1 may act as a novel bHLH transcriptional repressor in SRF signaling pathway to mediate cellular functions. (c) 2006 Elsevier Inc. All rights reserved.