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Two potent transactivation domains in the C‐terminal region of human NANOG mediate transcriptional activation in human embryonic carcinoma cells
Author(s) -
Do HyunJin,
Lee WonYoung,
Lim HyeYoung,
Oh JongHyun,
Kim DongKu,
Kim JinHoi,
Kim Teoan,
Kim JaeHwan
Publication year - 2009
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22089
Subject(s) - homeobox protein nanog , sox2 , transactivation , carcinogenesis , embryonic stem cell , biology , transcription factor , microbiology and biotechnology , nanog homeobox protein , induced pluripotent stem cell , stem cell , transfection , hek 293 cells , cell culture , gene , genetics
The core embryonic stem 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. © 2009 Wiley‐Liss, Inc.