同源框蛋白質NANOG

同源框蛋白質NANOG
已知的結構
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	2KT0
識別號
别名	NANOG；, entrez:79923, Nanog, Nanog homeobox
外部ID	OMIM：607937 MGI：1919200 HomoloGene：78027 GeneCards：NANOG
基因位置（人类）
染色体	12號染色體[1]
终止	7,799,146 bp[1]
基因位置（小鼠）
染色体	小鼠6号染色体[2]
终止	122,691,592 bp[2]
RNA表达模式
	查阅更多表达数据
基因本體
分子功能	• DNA结合转录因子活性; • DNA结合; • sequence-specific DNA binding; • 血浆蛋白结合; • transcription corepressor activity; • RNA polymerase II transcription regulatory region sequence-specific DNA binding; • DNA-binding transcription activator activity, RNA polymerase II-specific; • DNA-binding transcription factor activity, RNA polymerase II-specific; • RNA polymerase II cis-regulatory region sequence-specific DNA binding;
細胞組分	• 核仁; • 细胞核; • 核质;
生物學過程	• 基因調節; • regulation of cell differentiation; • multicellular organism development; • 细胞分化; • 細胞增殖; • regulation of transcription, DNA-templated; • somatic stem cell population maintenance; • transcription, DNA-templated; • positive regulation of transcription by RNA polymerase II; • endodermal cell fate specification; • negative regulation of nucleic acid-templated transcription; • stem cell population maintenance; • transcription by RNA polymerase II; • cytokine-mediated signaling pathway; • regulation of transcription by RNA polymerase II; • positive regulation of stem cell proliferation;
	Sources:Amigo / QuickGO
直系同源
	79923
	71950
	ENSG00000111704
	ENSMUSG00000012396
	Q9H9S0
	Q80Z64
	NM_001297698; NM_024865
	NM_028016; NM_001289828; NM_001289830; NM_001289831
	NP_001284627; NP_079141
	NP_001276757; NP_001276759; NP_001276760; NP_082292
	維基數據

NANOG（讀法：nanOg）是一种对未分化的胚胎干细胞（ESC）自我更新至关重要的转录因子。人体的NANOG蛋白质由NANOG基因编码[5][6]。

结构

人类NANOG蛋白质是一种长305氨基酸残基的蛋白质，拥有一个长约60氨基酸残基的DNA结合同源域（homeodomain, HD）以及一个无规则的N端。NANOG的同源结构域由三个α螺旋以及一些连结这些α螺旋的环结构组成。尽管Nanog蛋白在脊椎动物中保守性不强，但是其同源结构域却拥有很强保守性[7][8]。

功能

NANOG对胚胎干细胞幹性的维持至关重要。NANOG能够与Sox2、Oct4共同作用，通过形成一个表达特异基因的转录网络，维持胚胎干细胞的自我更新能力，並抑制胚胎干细胞的分化[9][10]。

胚胎干细胞的转录流程

研究進展

基础生物学理论

鼠胚胎幹細胞中Nanog的過表達能够使这类细胞能够在无白血病抑制因子（Leukemia inhibitory factor, LIF）的环境中维持的自我更新能力[11]，过表达NANOG的人胚胎干细胞能够在多次传代后仍然保持幹性。敲低Nanog基因的表达能够促进胚胎干细胞的分化[12]。

如果Nanog蛋白不表达或失去功能，鼠胚胎干细胞会分化成其他类型的细胞[5][6][13]。

已证明肿瘤抑制因子p53能够与NANOG基因的启动子结合，并能够在鼠胚胎干细胞DNA受损後抑制NANOG基因的表达。因此，p53能够通过p53依赖细胞周期阻滞以及自噬诱导胚胎干细胞的分化[13]。

Nanog基因能够使得NIH3T3细胞的生长加快，并表现出能够在软琼脂上形成细胞集落等等与原来不同的特性[14]。

一部分肿瘤细胞或肿瘤幹细胞会表达NANOG蛋白[15][16]。

进化生物学

人类和黑猩猩的基因組共享10个位置相同的NANOG蛋白假基因，其中一个是基因重複造成，另外九个为逆转录產生的假基因（retropseudogenes）。在九个NANOG逆转录假基因中，有两个缺乏Poly-A尾，说明在它们的产生过程中可能发生了复制错误。且因为同一种假基因在两个不相关的基因组中出現，還包含相同複製錯誤的機會極低，此一事实提供了一个人与黑猩猩之间演化的證據[17]。

命名

成功分离鼠Nanog基因的伊恩·钱伯斯（Ian Chambers）教授这样说：「Nanog似乎是一种拥有决定胚胎干细胞能在实验室中生长的能力的基因，也就是说它能够使得干细胞『长生不老』，因此，我用「Tír na nÓg」（提爾納諾，爱尔兰神话中的异世界）来命名这种蛋白质/基因。」[18]。

参考文献

GRCh38: Ensembl release 89: ENSG00000111704 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000012396 - Ensembl, May 2017
. National Center for Biotechnology Information, U.S. National Library of Medicine.
. National Center for Biotechnology Information, U.S. National Library of Medicine.
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Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, Smith A. . Cell. May 2003, 113 (5): 643–55. PMID 12787505. doi:10.1016/S0092-8674(03)00392-1.
Gehring WJ et al. . Cell. 1994, 78 (2): 211–223.
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. NCBI. [2016-12-18]. （原始内容存档于2020-09-22）.
Boiani M, Schöler HR. . Nat Rev Mol Cell Biol. 2005-12, 6 (11): 872–84.
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Gong, Shuai et al. . Molecular Carcinogenesis 54.9(2015):679–687.
Hoei-Hansen CE, Almstrup K, Nielsen JE, Brask Sonne S, Graem N, Skakkebaek NE, Leffers H, Rajpert-De Meyts E. . Histopathology. Jul 2005, 47 (1): 48–56. PMID 15982323. doi:10.1111/j.1365-2559.2005.02182.x.
Daniel J. Fairbanks. . Buffalo, N.Y: Prometheus Books. 2007: 94–96, 177–182. ISBN 1-59102-564-8.
. [2007-07-26]. （原始内容存档于2012-03-25）.

延伸阅读

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外部链接

醫學主題詞表（MeSH）：NANOG+protein,+human
醫學主題詞表（MeSH）：Nanog+protein,+mouse
FactorBook NANOG
. Young Lab. Whitehead Institute for Biomedical Research. [2009-02-28]. （原始内容存档于2009-06-28）.
. Whitehead Institute. [2009-02-28]. （原始内容存档于2012-06-26）.
Discovery reveals more about stem cells' immortality

参见

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000111704 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000012396 - Ensembl, May 2017

[3] . National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] . National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid12787504-5] Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K, Maruyama M, Maeda M, Yamanaka S. . Cell. May 2003, 113 (5): 631–42. PMID 12787504. doi:10.1016/S0092-8674(03)00393-3.

[pmid12787505-6] Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, Smith A. . Cell. May 2003, 113 (5): 643–55. PMID 12787505. doi:10.1016/S0092-8674(03)00392-1.

[7] Gehring WJ et al. . Cell. 1994, 78 (2): 211–223.

[8] Gehring WJ, Affolter M, Bürglin T. . Annu Rev Biochem. 1994, (63): 487–526.

[9] . NCBI. [2016-12-18]. （原始内容存档于2020-09-22）.

[10] Boiani M, Schöler HR. . Nat Rev Mol Cell Biol. 2005-12, 6 (11): 872–84.

[pmid16501172-11] Darr H, Mayshar Y, Benvenisty N. . Development. Mar 2006, 133 (6): 1193–201. PMID 16501172. doi:10.1242/dev.02286.

[pmid15749924-12] Zaehres H, Lensch MW, Daheron L, Stewart SA, Itskovitz-Eldor J, Daley GQ. . Stem Cells. Mar 2005, 23 (3): 299–305. PMID 15749924. doi:10.1634/stemcells.2004-0252.

[pmid15619621-13] Lin T, Chao C, Saito S, Mazur SJ, Murphy ME, Appella E, Xu Y. . Nature Cell Biology. Feb 2005, 7 (2): 165–71. PMID 15619621. doi:10.1038/ncb1211.

[pmid16540082-14] Piestun D, Kochupurakkal BS, Jacob-Hirsch J, Zeligson S, Koudritsky M, Domany E, Amariglio N, Rechavi G, Givol D. . Biochemical and Biophysical Research Communications. Apr 2006, 343 (1): 279–85. PMID 16540082. doi:10.1016/j.bbrc.2006.02.152.

[15] Gong, Shuai et al. . Molecular Carcinogenesis 54.9(2015):679–687.

[pmid15982323-16] Hoei-Hansen CE, Almstrup K, Nielsen JE, Brask Sonne S, Graem N, Skakkebaek NE, Leffers H, Rajpert-De Meyts E. . Histopathology. Jul 2005, 47 (1): 48–56. PMID 15982323. doi:10.1111/j.1365-2559.2005.02182.x.

[isbn1-59102-564-8-17] Daniel J. Fairbanks. . Buffalo, N.Y: Prometheus Books. 2007: 94–96, 177–182. ISBN 1-59102-564-8.

[18] . [2007-07-26]. （原始内容存档于2012-03-25）.