Cai Zhenyu, Wang Yuequn, Yu Weishi, Xiao Jing, Li Yongqing, Liu Lian, Zhu Chuanbing, Tan Kunrong, Deng Yun, Yuan Wuzhou, Liu Mingyao, Wu Xiushan
The Center for Heart Development, College of Life Sciences, Hunan Normal University, Changsha, 410081 Hunan, PR China.
Biochem Biophys Res Commun. 2006 May 12;343(3):973-81. doi: 10.1016/j.bbrc.2006.02.187. Epub 2006 Mar 13.
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.
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）。预测的蛋白质在N端和C端分别包含一个bHLH结构域和一个DUF654结构域。Northern印迹分析表明，一个2.3-kb的转录本在人类早期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较高。当与GAL4 DNA结合结构域融合并与VP-16共转染时，hnulp1是一种转录抑制因子，其中DUF654基序代表基础转录抑制活性。用曲古抑菌素A处理细胞可以缓解这种抑制作用，这表明DUF654基序通过增加GAL4驱动启动子处的去乙酰化酶活性发挥作用。hnulp1蛋白在COS-7细胞中的过表达抑制了血清反应因子（SRF）的转录活性，这表明hnulp1可能作为SRF信号通路中的一种新型bHLH转录抑制因子来介导细胞功能。
