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同源框蛋白質NANOG

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NANOG
已知的結構
PDB Ortholog search: PDBe RCSB
識別號
别名 NANOG;Nanog、​Nanog homeobox、​entrez:79923
外部ID OMIM607937 MGI1919200 HomoloGene78027 GeneCardsNANOG
RNA表达模式
PBB GE NANOG 220184 at fs.png
更多參考(基因)表达數據
直系同源
物種 人類 小鼠
Entrez
Ensembl
UniProt
mRNA​序列

XM_011520852、NM_001297698、NM_024865、XM_011520850

NM_028016、NM_001289828、NM_001289830、NM_001289831、XM_006506651、XM_011241473

蛋白序列

NP_001284627、NP_079141、XP_011519152、XP_011519154

NP_001276757、NP_001276759、NP_001276760、NP_082292、XP_006506714、XP_011239775

基因位置​(UCSC) Chr 12: 7.79 – 7.8 Mb n/a
PubMed​查找 [1] [2]
維基數據
檢視/編輯 人類 檢視/編輯 小鼠

NANOG(讀法:nanOg)是一种对未分化胚胎干细胞(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[3][4]

结构[编辑]

人类NANOG蛋白质是一种长305氨基酸残基蛋白质,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[5][6]

功能[编辑]

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[7][8]

研究進展[编辑]

基础生物学理论[编辑]

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[9],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[10]

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[3][4][11]

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[11]

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[12]

一部分肿瘤细胞或肿瘤幹细胞会表达NANOG蛋白[13][14]

进化生物学[编辑]

人类黑猩猩拥有10个位置相同的NANOG蛋白假基因,其中一个是,另外九个为逆转录假基因。在九个NANOG逆转录假基因中,两个缺乏逆绝大部分转录假基因都有的Poly(A)尾,说明在它们的产生过程中可能发生了复制错误。因为同一种假基因(包含复制错误的)在两个不相关的基因组中不太可能存在于同一位点,这一事实提供了一个人与黑猩猩之间演化的證據[15]

命名[编辑]

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。」[16]

参考文献[编辑]

  1. ^ Human PubMed Reference:. 
  2. ^ Mouse PubMed Reference:. 
  3. ^ 3.0 3.1 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. 
  4. ^ 4.0 4.1 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. 
  5. ^ Gehring WJ 等. Homeodomain-DNA recognition. Cell. 1994, 78 (2): 211–223. 
  6. ^ Gehring WJ, Affolter M, Bürglin T. Homeodomain protein. Annu Rev Biochem. 1994, (63): 487–526. 
  7. ^ NANOG Nanog homeobox [ Homo sapiens (human) ]. NCBI. [2016-12-18]. 
  8. ^ Boiani M, Schöler HR. Regulatory networks in embryo-derived pluripotent stem cells. Nat Rev Mol Cell Biol. 2005-12, 6 (11): 872–84. 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ 11.0 11.1 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. 
  12. ^ 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. 
  13. ^ Gong, Shuai 等. Regulation of NANOG in cancer cells.. Molecular Carcinogenesis 54.9(2015):679–687. 
  14. ^ 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. 
  15. ^ 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. 
  16. ^ ScienceDaily: Cells Of The Ever Young: Getting Closer To The Truth. [2007-07-26]. 

拓展阅读[编辑]

  • 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[编辑]

参见[编辑]