白血病抑制因子

Leukemia inhibitory factor
白血病抑制因子
Leukemia inhibitory factor; 白血病抑制因子
	PDB rendering based on 1LKI.
有效结构
PDB	直系同源检索：PDBe, RCSB
PDB查询代码列表
	1EMR, 1PVH, 2Q7N
标识
代号	LIF; CDF; DIA; HILDA; MLPLI
扩展标识	遗传学：159540 鼠基因：96787 同源基因：1734 GeneCards: LIF Gene
基因本体论描述
分子功能	· RNA polymerase II transcription factor recruiting transcription factor activity; · receptor binding; · cytokine activity; · leukemia inhibitory factor receptor binding; · growth factor activity;
细胞成分	· extracellular space; · cytoplasm;
生物过程	· blood vessel remodeling; · immune response; · multicellular organismal development; · embryo implantation; · positive regulation of cell proliferation; · negative regulation of cell proliferation; · stem cell maintenance; · positive regulation of peptidyl-serine phosphorylation; · positive regulation of peptidyl-serine phosphorylation of STAT protein; · tyrosine phosphorylation of Stat3 protein; · positive regulation of tyrosine phosphorylation of Stat1 protein; · positive regulation of tyrosine phosphorylation of Stat3 protein; · positive regulation of MAPK cascade; · positive regulation of macrophage differentiation; · negative regulation of meiosis; · positive regulation of transcription from RNA polymerase II promoter; · decidualization; · negative regulation of hormone secretion; · lung alveolus development; · muscle organ morphogenesis; · neuron development; · positive regulation of astrocyte differentiation; · leukemia inhibitory factor signaling pathway; · positive regulation of peptidyl-tyrosine phosphorylation; · lung vasculature development; · lung lobe morphogenesis; · trophoblast giant cell differentiation; · spongiotrophoblast differentiation; · negative regulation of ERK1 and ERK2 cascade; · positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis; · regulation of metanephric nephron tubule epithelial cell differentiation; · positive regulation of protein localization to nucleus; · positive regulation of histone H3-K27 acetylation;
	Sources: Amigo / QuickGO
RNA表达模式
	更多表达数据
直系同源体
物种	人类
Entrez	3976
Ensembl	ENSG00000128342
UniProt	P15018
mRNA序列	NM_001257135
蛋白序列	NP_001244064
基因位置	Chr 22:; 30.64 – 30.64 Mb
PubMed查询	[1]
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白血病抑制因子（Leukemia inhibitory factor，缩写 LIF）是一种属于白介素-6大类的细胞因子。它能通过抑制分化影响细胞生长。LIF水平下降会使细胞开始分化。

Quick Facts Leukemia inhibitory factor 白血病抑制因子, 有效结构 ...

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功能

白血病抑制因子能够诱导骨髓性白血病细胞的末端分化，进而阻止其生长，因而得名。白血病抑制因子还有以下功能：能促进多种细胞的生长与分化，影响骨代谢、恶病质体、神经发育（英语：Neural development），胚胎发育以及炎症作用。受p53调控的白血病抑制因子能促进小鼠和人的胚胎着床^[1]。一篇文章提出重组人白血病抑制因子可能可以提高意外怀孕的妇女（体内胚胎）的着床成功率^[2]。

表达

LIF在正常情况下会由囊胚中的滋养层（TE）表达，而其受体LIFR则会由内细胞群（ICM）的细胞表达。胚胎干细胞取自内细胞群的细胞，在体外培养时就需要额外补充LIF。目前，重组LIF已可以通过基因工程的手段由植物（水稻）产生^[3]。

干细胞培养

干细胞培养基中大都含有LIF，可用于替代喂养层（feeder layer）细胞，因为喂养层细胞的主要作用即产生LIF。不表达LIF基因的喂养层细胞难以支持干细胞的培养^[4]。LIF通过招募信号诱导分子以及转录激活因子3（STAT3）促进细胞的自我更新。活化的LIFR能征募Stat3。随后，JAK激酶能将其磷酸化。不过LIF和Stat3是不足以阻止细胞分化的，一旦移去培养基中的血清，干细胞就会分化。在原生多能性干细胞分化的可逆阶段，加入LIF可以使细胞重回原生多能性阶段^[5]^[6]^[7]。

参考

[1]
Wenwei Hu, Zhaohui Feng, Angelika K. Teresky1, Arnold J. Levine. p53 regulates maternal reproduction through LIF. Nature. November 29, 2007, 450 (7170): 721–724 [2017-01-27]. PMID 18046411. doi:10.1038/nature05993. （原始内容存档于2017-03-15）.
[2]
Aghajanova, L. Leukemia inhibitory factor and human embryo implantation. Annals of the New York Academy of Sciences. 2004, 1034: 176–83. PMID 15731310. doi:10.1196/annals.1335.020.
[3]
Bradford A. Youngblood; et al. Application of recombinant human leukemia inhibitory factor (LIF) produced in rice (Oryza sativa L.) for maintenance of mouse embryonic stem cells. Journal of Biotechnology Volume 172. 2014-02-20: 67–72.
[4]
Stewart, C. L.; Kaspar, P; Brunet, L. J.; Bhatt, H; Gadi, I; Köntgen, F; Abbondanzo, S. J. Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor. Nature. 1992, 359 (6390): 76–9. PMID 1522892. doi:10.1038/359076a0.
[5]
Martello, Graziano; Smith, Austin. The Nature of Embryonic Stem Cells. Annual Review Cell Developmental Biology. 2014, 30: 647. doi:10.1146/annurev-cellbio-100913-013116.
[6]
Kawahara Y, Manabe T, Matsumoto M, Kajiume T, Matsumoto M, Yuge L. Zwaka, Thomas , 编. LIF-Free Embryonic Stem Cell Culture in Simulated Microgravity. PLoS ONE. 2009, 4 (7): e6343 [2017-01-27]. PMC 2710515 . PMID 19626124. doi:10.1371/journal.pone.0006343. （原始内容存档于2014-02-22）.
[7]
CGS : PTO Finds Stem Cell Patent Anticipated, Obvious in Light of 'Significant Guideposts'. （原始内容存档于2011-10-04）.

拓展阅读

Patterson PH. Leukemia inhibitory factor, a cytokine at the interface between neurobiology and immunology. Proc. Natl. Acad. Sci. U.S.A. 1994, 91 (17): 7833–5. PMC 44497 . PMID 8058719. doi:10.1073/pnas.91.17.7833.
Aghajanova L. Leukemia inhibitory factor and human embryo implantation. Ann. N. Y. Acad. Sci. 2005, 1034: 176–83. PMID 15731310. doi:10.1196/annals.1335.020.
Králícková M, Síma P, Rokyta Z. Role of the leukemia-inhibitory factor gene mutations in infertile women: the embryo-endometrial cytokine cross talk during implantation--a delicate homeostatic equilibrium. Folia Microbiol. (Praha). 2005, 50 (3): 179–86. PMID 16295654. doi:10.1007/BF02931563.
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Moreau JF, Donaldson DD, Bennett F; et al. Leukaemia inhibitory factor is identical to the myeloid growth factor human interleukin for DA cells. Nature. 1989, 336 (6200): 690–2. PMID 3143918. doi:10.1038/336690a0.
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