同源框蛋白质NANOG

同源框蛋白质NANOG
已知的结构
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	2KT0
识别号
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号染色体
终止	7,799,146 bp
基因位置（小鼠）
染色体	小鼠6号染色体
终止	122,691,592 bp
RNA表达模式
	查阅更多表达数据
基因本体
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;
细胞组分	• 核仁; • 细胞核; • 核质;
生物学过程	• 基因调节; • regulation of cell differentiation; • multicellular organism development; • 细胞分化; • 细胞增殖; • 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
	维基数据
查看/编辑人类	查看/编辑小鼠

NANOG（读法：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]。

Quick Facts 同源框蛋白质NANOG, 已知的结构 ...

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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对胚胎干细胞干性的维持至关重要。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，并抑制胚胎干细胞的分化^[9]^[10]。

研究进展

基础生物学理论

鼠胚胎干细胞中Nanog的过表达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干性。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受损后抑制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干细胞会表达NANOG蛋白^[15]^[16]。

进化生物学

人类和黑猩猩的基因组共享10个位置相同的NANOG蛋白假基因，其中一个是基因重复造成，另外九个为逆转录产生的假基因（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现，还包含相同复制错误的机会极低，此一事实提供了一个人与黑猩猩之间演化的证据^[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”（提尔纳诺，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

[1]
GRCh38: Ensembl release 89: ENSG00000111704 - Ensembl, May 2017
[2]
GRCm38: Ensembl release 89: ENSMUSG00000012396 - Ensembl, May 2017
[3]
Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
[4]
Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
[5]
Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K, Maruyama M, Maeda M, Yamanaka S. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell. May 2003, 113 (5): 631–42. PMID 12787504. doi:10.1016/S0092-8674(03)00393-3.
[6]
Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, Smith A. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell. May 2003, 113 (5): 643–55. PMID 12787505. doi:10.1016/S0092-8674(03)00392-1.
[7]
Gehring WJ et al. Homeodomain-DNA recognition. Cell. 1994, 78 (2): 211–223.
[8]
Gehring WJ, Affolter M, Bürglin T. Homeodomain protein. Annu Rev Biochem. 1994, (63): 487–526.
[9]
NANOG Nanog homeobox [ Homo sapiens (human) ]. NCBI. [2016-12-18]. （原始内容存档于2020-09-22）.
[10]
Boiani M, Schöler HR. Regulatory networks in embryo-derived pluripotent stem cells. Nat Rev Mol Cell Biol. 2005-12, 6 (11): 872–84.
[11]
Darr H, Mayshar Y, Benvenisty N. Overexpression of NANOG in human ES cells enables feeder-free growth while inducing primitive ectoderm features. Development. Mar 2006, 133 (6): 1193–201. PMID 16501172. doi:10.1242/dev.02286.
[12]
Zaehres H, Lensch MW, Daheron L, Stewart SA, Itskovitz-Eldor J, Daley GQ. High-efficiency RNA interference in human embryonic stem cells. Stem Cells. Mar 2005, 23 (3): 299–305. PMID 15749924. doi:10.1634/stemcells.2004-0252.
[13]
Lin T, Chao C, Saito S, Mazur SJ, Murphy ME, Appella E, Xu Y. p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression. Nature Cell Biology. Feb 2005, 7 (2): 165–71. PMID 15619621. doi:10.1038/ncb1211.
[14]
Piestun D, Kochupurakkal BS, Jacob-Hirsch J, Zeligson S, Koudritsky M, Domany E, Amariglio N, Rechavi G, Givol D. Nanog transforms NIH3T3 cells and targets cell-type restricted genes. 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. Regulation of NANOG in cancer cells.. Molecular Carcinogenesis 54.9(2015):679–687.
[16]
Hoei-Hansen CE, Almstrup K, Nielsen JE, Brask Sonne S, Graem N, Skakkebaek NE, Leffers H, Rajpert-De Meyts E. Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma in situ and germ cell tumours. Histopathology. Jul 2005, 47 (1): 48–56. PMID 15982323. doi:10.1111/j.1365-2559.2005.02182.x.
[17]
Daniel J. Fairbanks. Relics of Eden: The Powerful Evidence of Evolution in Human DNA. Buffalo, N.Y: Prometheus Books. 2007: 94–96, 177–182. ISBN 1-59102-564-8.
[18]
ScienceDaily: Cells Of The Ever Young: Getting Closer To The Truth. [2007-07-26]. （原始内容存档于2012-03-25）.

延伸阅读

Cavaleri F, Schöler HR. Nanog: a new recruit to the embryonic stem cell orchestra. Cell. May 2003, 113 (5): 551–2. PMID 12787492. doi:10.1016/S0092-8674(03)00394-5.
Constantinescu S. Stemness, fusion and renewal of hematopoietic and embryonic stem cells. Journal of Cellular and Molecular Medicine. 2004, 7 (2): 103–12. PMID 12927049. doi:10.1111/j.1582-4934.2003.tb00209.x.
Pan G, Thomson JA. Nanog and transcriptional networks in embryonic stem cell pluripotency. Cell Research. Jan 2007, 17 (1): 42–9. PMID 17211451. doi:10.1038/sj.cr.7310125.
Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K, Maruyama M, Maeda M, Yamanaka S. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell. May 2003, 113 (5): 631–42. PMID 12787504. doi:10.1016/S0092-8674(03)00393-3.
Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, Smith A. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell. May 2003, 113 (5): 643–55. PMID 12787505. doi:10.1016/S0092-8674(03)00392-1.
Clark AT, Rodriguez RT, Bodnar MS, Abeyta MJ, Cedars MI, Turek PJ, Firpo MT, Reijo Pera RA. Human STELLAR, NANOG, and GDF3 genes are expressed in pluripotent cells and map to chromosome 12p13, a hotspot for teratocarcinoma. Stem Cells. 2004, 22 (2): 169–79. PMID 14990856. doi:10.1634/stemcells.22-2-169.
Hart AH, Hartley L, Ibrahim M, Robb L. Identification, cloning and expression analysis of the pluripotency promoting Nanog genes in mouse and human. Developmental Dynamics. May 2004, 230 (1): 187–98. PMID 15108323. doi:10.1002/dvdy.20034.
Booth HA, Holland PW. Eleven daughters of NANOG. Genomics. Aug 2004, 84 (2): 229–38. PMID 15233988. doi:10.1016/j.ygeno.2004.02.014.
Hatano SY, Tada M, Kimura H, Yamaguchi S, Kono T, Nakano T, Suemori H, Nakatsuji N, Tada T. Pluripotential competence of cells associated with Nanog activity. Mechanisms of Development. Jan 2005, 122 (1): 67–79. PMID 15582778. doi:10.1016/j.mod.2004.08.008.
Deb-Rinker P, Ly D, Jezierski A, Sikorska M, Walker PR. Sequential DNA methylation of the Nanog and Oct-4 upstream regions in human NT2 cells during neuronal differentiation. The Journal of Biological Chemistry. Feb 2005, 280 (8): 6257–60. PMID 15615706. doi:10.1074/jbc.C400479200.
Zaehres H, Lensch MW, Daheron L, Stewart SA, Itskovitz-Eldor J, Daley GQ. High-efficiency RNA interference in human embryonic stem cells. Stem Cells. Mar 2005, 23 (3): 299–305. PMID 15749924. doi:10.1634/stemcells.2004-0252.
Hoei-Hansen CE, Almstrup K, Nielsen JE, Brask Sonne S, Graem N, Skakkebaek NE, Leffers H, Rajpert-De Meyts E. Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma in situ and germ cell tumours. Histopathology. Jul 2005, 47 (1): 48–56. PMID 15982323. doi:10.1111/j.1365-2559.2005.02182.x.
Hyslop L, Stojkovic M, Armstrong L, Walter T, Stojkovic P, Przyborski S, Herbert M, Murdoch A, Strachan T, Lako M. Downregulation of NANOG induces differentiation of human embryonic stem cells to extraembryonic lineages. Stem Cells. Sep 2005, 23 (8): 1035–43. PMID 15983365. doi:10.1634/stemcells.2005-0080.
Oh JH, Do HJ, Yang HM, Moon SY, Cha KY, Chung HM, Kim JH. Identification of a putative transactivation domain in human Nanog. Experimental & Molecular Medicine. Jun 2005, 37 (3): 250–4. PMID 16000880. doi:10.1038/emm.2005.33.
Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, Guenther MG, Kumar RM, Murray HL, Jenner RG, Gifford DK, Melton DA, Jaenisch R, Young RA. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell. Sep 2005, 122 (6): 947–56. PMC 3006442 . PMID 16153702. doi:10.1016/j.cell.2005.08.020.
Kim JS, Kim J, Kim BS, Chung HY, Lee YY, Park CS, Lee YS, Lee YH, Chung IY. Identification and functional characterization of an alternative splice variant within the fourth exon of human nanog. Experimental & Molecular Medicine. Dec 2005, 37 (6): 601–7. PMID 16391521. doi:10.1038/emm.2005.73.
Darr H, Mayshar Y, Benvenisty N. Overexpression of NANOG in human ES cells enables feeder-free growth while inducing primitive ectoderm features. Development. Mar 2006, 133 (6): 1193–201. PMID 16501172. doi:10.1242/dev.02286.

外部链接

医学主题词表（MeSH）：NANOG+protein,+human
医学主题词表（MeSH）：Nanog+protein,+mouse
FactorBook NANOG
Core Transcriptional Regulatory Circuitry in Human Embryonic Stem Cells. Young Lab. Whitehead Institute for Biomedical Research. [2009-02-28]. （原始内容存档于2009-06-28）.
Jaenisch Lab Research Summary. Whitehead Institute. [2009-02-28]. （原始内容存档于2012-06-26）.
Discovery reveals more about stem cells' immortality

参见

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

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

[3] [3]
Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] [4]
Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid12787504-5] [5]
Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K, Maruyama M, Maeda M, Yamanaka S. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell. May 2003, 113 (5): 631–42. PMID 12787504. doi:10.1016/S0092-8674(03)00393-3.

[pmid12787505-6] [6]
Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, Smith A. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell. May 2003, 113 (5): 643–55. PMID 12787505. doi:10.1016/S0092-8674(03)00392-1.

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

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

[9] [9]
NANOG Nanog homeobox [ Homo sapiens (human) ]. NCBI. [2016-12-18]. （原始内容存档于2020-09-22）.

[10] [10]
Boiani M, Schöler HR. Regulatory networks in embryo-derived pluripotent stem cells. Nat Rev Mol Cell Biol. 2005-12, 6 (11): 872–84.

[pmid16501172-11] [11]
Darr H, Mayshar Y, Benvenisty N. Overexpression of NANOG in human ES cells enables feeder-free growth while inducing primitive ectoderm features. Development. Mar 2006, 133 (6): 1193–201. PMID 16501172. doi:10.1242/dev.02286.

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

[pmid15619621-13] [13]
Lin T, Chao C, Saito S, Mazur SJ, Murphy ME, Appella E, Xu Y. p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression. Nature Cell Biology. Feb 2005, 7 (2): 165–71. PMID 15619621. doi:10.1038/ncb1211.

[pmid16540082-14] [14]
Piestun D, Kochupurakkal BS, Jacob-Hirsch J, Zeligson S, Koudritsky M, Domany E, Amariglio N, Rechavi G, Givol D. Nanog transforms NIH3T3 cells and targets cell-type restricted genes. Biochemical and Biophysical Research Communications. Apr 2006, 343 (1): 279–85. PMID 16540082. doi:10.1016/j.bbrc.2006.02.152.

[15] [15]
Gong, Shuai et al. Regulation of NANOG in cancer cells.. Molecular Carcinogenesis 54.9(2015):679–687.

[pmid15982323-16] [16]
Hoei-Hansen CE, Almstrup K, Nielsen JE, Brask Sonne S, Graem N, Skakkebaek NE, Leffers H, Rajpert-De Meyts E. Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma in situ and germ cell tumours. Histopathology. Jul 2005, 47 (1): 48–56. PMID 15982323. doi:10.1111/j.1365-2559.2005.02182.x.

[isbn1-59102-564-8-17] [17]
Daniel J. Fairbanks. Relics of Eden: The Powerful Evidence of Evolution in Human DNA. Buffalo, N.Y: Prometheus Books. 2007: 94–96, 177–182. ISBN 1-59102-564-8.

[18] [18]
ScienceDaily: Cells Of The Ever Young: Getting Closer To The Truth. [2007-07-26]. （原始内容存档于2012-03-25）.

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