Two Potent Transactivation Domains in the C-Terminal Region of Human NANOG Mediate Transcriptional Activation in Human Embryonic Carcinoma Cells
Two Potent Transactivation Domains in the C-Terminal Region of Human NANOG Mediate Transcriptional Activation in Human Embryonic Carcinoma Cells
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DOI：
10.1002/jcb.22089
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发表时间：
2009-04-15
影响因子：
4
通讯作者：
Kim, Jae-Hwan
中科院分区：
文献类型：
--
作者：
Do, Hyun-Jin;Lee, Won-Young;Kim, Jae-Hwan
核心胚胎干细胞转录因子Oct4、Sox2和Nanog在生殖细胞肿瘤（gct）中表达，并被认为在肿瘤发生中发挥调节作用。然而，这些蛋白的复杂网络调控肿瘤发生的机制尚不清楚。Nanog是一种新型的含有同源盒的转录因子，在多能细胞和gct中表达。为了了解人类NANOG （hNANOG）在生殖细胞中的分子和功能作用，研究人员对hNANOG的c端结构域（CD）进行了诱变，并在NCCIT人胚胎癌细胞中进行了瞬时转染实验，以确定关键的转激活基序。我们将CD分为三个假定的功能亚域，CD1，色氨酸重复（WR）亚域和CD2。WR亚域和CD2各自具有转录潜能，两者结合对转录活性具有协同作用，而CD1则不具有转录活性。hNANOG CD的最大和协同转录激活需要WR亚域的谷氨酰胺基序和CD2中的多个酸性残基。目前的研究结果有助于更好地理解干细胞转录因子的复杂分子机制及其在生殖细胞肿瘤发生过程中不受调节的增殖中的作用。j .细胞。生物化学学报，26(6):1079-1089,2009。(c) 2009 Wiley-Liss, Inc。
The core embryonic stern cell transcription factors Oct4, Sox2, and Nanog are expressed in germ cell tumors (GCTs) and have been proposed to play a regulatory role in tumorigenesis. However, little is known about the mechanism of regulation of tumorigenesis by the complicated network of these proteins. Nanog is a novel homeobox-containing transcription factor that is expressed in pluripotent cells as well as GCTs. To understand the molecular and functional role of human NANOG (hNANOG) in germ cells, mutagenesis of the C-terminal domain (CD) of hNANOG and transient transfection assays in NCCIT human embryonic carcinoma cells were carried out to identify critical transactivation motifs. We divided the CD into three putative functional subdomains, CD1, tryptophan-repeat (WR) subdomain, and CD2. WR subdomain and CD2 independently contained transcriptional potential and, in combination, had a synergistic effect on transcriptional activity, while CD1 was transcriptionally inactive. The glutamine (Q) motif in WR subdomain, and multiple acidic residues in CD2 were required For maximal and synergistic transcriptional activation by the hNANOG CD. The results of the current study contribute to a better understanding of the complicated molecular machinery of stem cell transcription factors and their role in unregulated proliferation in germ cell tumorigenesis. J. Cell. Biochem. 106: 1079-1089, 2009. (c) 2009 Wiley-Liss, Inc.