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	The C-terminal Pentapeptide of Nanog Tryptophan Repeat Domain Interacts with Nac1 and Regulates Stem Cell Proliferation but Not Pluripotency
	Ma, Tianhua ; Wang, Zhe ; Guo, Yunqian ; Pei, Duanqing
	2010-10-12 ; 2010-10-12
关键词	SELF-RENEWAL SUSTAINING FACTOR MOUSE TRANSCRIPTION EXPRESSION NETWORK PROTEIN IDENTIFICATION GENERATION CLONING Biochemistry & Molecular Biology
中文摘要	Overexpression of Nanog in mouse embryonic stem (ES) cells has been shown to abrogate the requirement of leukemia inhibitory factor for self-renewal in culture. Little is known about the molecular mechanism of Nanog function. Here we describe the role of the tryptophan repeat (WR) domain, one of the two transactivators at its C terminus, in regulating stem cell proliferation as well as pluripotency. We first created a supertransactivator, W2W3x10, by duplicating repeats W2W3 10 times and discovered that it can functionally substitute for wild type WR at sustaining pluripotency, albeit with a significantly slower cell cycle, phenocopying Nanog(9W) with the C-terminal pentapeptide (WNAAP) of WR deleted. ES cells carrying both W2W3x10 and Nanog(9W) have a longer G(1) phase, a shorter S phase in cell cycle distribution and progression analysis, and a lower level of pAkt(Ser(473)) compared with wild type Nanog, suggesting that both mutants impact the cell cycle machinery via the phosphatidylinositol 3-kinase/Akt pathway. Both mutants remain competent in dimerizing with Nanog but cannot form a complex with Nac1 efficiently, suggesting that WNAAP may be involved in Nac1 binding. By tagging Gal4DBD with WNAAP, we demonstrated that this pentapeptide is sufficient to confer Nac1 binding. Furthermore, we can rescue W2W3x10 by placing WNAAP at the corresponding locations. Finally, we found that Nanog and Nac1 synergistically up-regulate ERas expression and promote the proliferation of ES cells. These results suggest that Nanog interacts with Nac1 through WNAAP to regulate the cell cycle of ES cells via the ERas/phosphatidylinositol 3-kinase/Akt pathway, but not pluripotency, thus decoupling cell cycle control from pluripotency.
语种	英语 ; 英语
出版者	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC ; BETHESDA ; 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
内容类型	期刊论文
源URL	[http://hdl.handle.net/123456789/81869]
专题	清华大学
推荐引用方式 GB/T 7714	Ma, Tianhua,Wang, Zhe,Guo, Yunqian,et al. The C-terminal Pentapeptide of Nanog Tryptophan Repeat Domain Interacts with Nac1 and Regulates Stem Cell Proliferation but Not Pluripotency[J],2010, 2010.
APA	Ma, Tianhua,Wang, Zhe,Guo, Yunqian,&Pei, Duanqing.(2010).The C-terminal Pentapeptide of Nanog Tryptophan Repeat Domain Interacts with Nac1 and Regulates Stem Cell Proliferation but Not Pluripotency..
MLA	Ma, Tianhua,et al."The C-terminal Pentapeptide of Nanog Tryptophan Repeat Domain Interacts with Nac1 and Regulates Stem Cell Proliferation but Not Pluripotency".(2010).

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