The protein ENH is a cytoplasmic sequestration factor for Id2 in normal and tumor cells from the nervous system
The protein ENH is a cytoplasmic sequestration factor for Id2 in normal and tumor cells from the nervous system
复制标题
DOI：
10.1073/pnas.0600168103
复制
发表时间：
2006-03-28
影响因子：
11.1
通讯作者：
Iavarone, A
中科院分区：
文献类型：
--
作者：
Lasorella, A;Iavarone, A
Id 2是碱性螺旋-环-螺旋转录因子和视网膜母细胞瘤肿瘤抑制蛋白的天然抑制剂。活性Id 2可防止神经系统的分化并促进细胞周期进展和肿瘤发生。在分化过程中调节Id 2活性的关键事件是从细胞核易位到细胞质。在这里，我们表明，肌动蛋白相关蛋白之谜同源物（ENH）是一个细胞质的保留因子Id 2。ENH含有三个LIM结构域，其在体外和体内与Id蛋白的螺旋-环-螺旋结构域结合。ENH在神经分化过程中上调，其在神经母细胞瘤细胞中的异位表达导致Id 2从细胞核易位到细胞质，从而使IQ的转录和细胞周期促进功能失活。相反，RNA干扰沉默ENH阻止了视黄酸分化的神经母细胞瘤细胞中Id 2的细胞质迁移。最后，分化的神经嵴源性肿瘤神经节神经母细胞瘤共表达Id 2和ENH的神经节细胞的细胞质中。这些数据表明，ENH有助于神经系统的分化，通过细胞质隔离的Id 2。他们还建议，ENH是一个抑制因子的Id蛋白的致癌活性在神经肿瘤。
Id2 is a natural inhibitor of the basic helix-loop-helix transcription factors and the retinoblastoma tumor suppressor protein. Active Id2 prevents differentiation and promotes cell-cycle progression and tumorigenesis in the nervous system. A key event that regulates Id2 activity during differentiation is translocation from the nucleus to the cytoplasm. Here we show that the actin-associated protein enigma homolog (ENH) is a cytoplasmic retention factor for Id2. ENH contains three LIM domains, which bind to the helix-loop-helix domain of Id proteins in vitro and in vivo. ENH is up-regulated during neural differentiation, and its ectopic expression in neuroblastoma cells leads to translocation of Id2 from the nucleus to the cytoplasm, with consequent inactivation of transcriptional and cell-cycle-promoting functions of IQ. Conversely, silencing of ENH by RNA interference prevents cytoplasmic relocation of Id2 in neuroblastoma cells differentiated with retinoic acid. Finally, the differentiated neural crest-derived tumor ganglioneuroblastoma coexpresses Id2 and ENH in the cytoplasm of ganglionic cells. These data indicate that ENH contributes to differentiation of the nervous system through cytoplasmic sequestration of Id2. They also suggest that ENH is a restraining factor of the oncogenic activity of Id proteins in neural tumors.