leukemia inhibitory factor leukemia inhibitory factor leukemia inhibitory factor, or lif, is an interleukin 6 class cytokine that affects cell growth by inhibiting differentiation. when lif levels drop, the cells differentiate. lifavailable structurespdbortholog search: pdbe rcsb list of pdb id codes1emr, 1pvh, 2q7nidentifiersaliaseslif, cdf, dia, hilda, mlpli, leukemia inhibitory factor, interleukin 6 family cytokine, lif interleukin 6 family cytokineexternal idsomim: 159540 mgi: 96787 homologene: 1734 genecards: lif gene location (human)chr.chromosome 22 (human)band22q12.2start30,240,453 bpend30,246,759 bpgene location (mouse)chr.chromosome 11 (mouse)band11 a1|11 2.94 cmstart4,207,557 bpend4,222,514 bprna expression patternbgeehumanmouse (ortholog)top expressed ingallbladdervena cavamucosa of urinary bladderappendixpancreatic ductal cellsmooth muscle tissueupper lobe of left lungrectumleft uterine tubeanterior pituitarytop expressed inendometriummucous glandmorulalipyolk sacesophagusjejunumduodenumcervixvastus lateralis musclemore reference expression databiogpsmore reference expression datagene ontologymolecular function signaling receptor binding growth factor activity cytokine activity protein binding leukemia inhibitory factor receptor binding cellular component extracellular region extracellular space cytosol biological process negative regulation of cell population proliferation stem cell differentiation positive regulation of peptidyl-serine phosphorylation of stat protein positive regulation of mapk cascade positive regulation of peptidyl-serine phosphorylation spongiotrophoblast differentiation lung development positive regulation of histone h3-k27 acetylation multicellular organism development lung lobe morphogenesis muscle organ morphogenesis maternal process involved in female pregnancy negative regulation of hormone secretion leukemia inhibitory factor signaling pathway regulation of metanephric nephron tubule epithelial cell differentiation regulation of cell differentiation positive regulation of gene expression stem cell population maintenance positive regulation of peptidyl-tyrosine phosphorylation regulation of rna polymerase ii regulatory region sequence-specific dna binding positive regulation of astrocyte differentiation negative regulation of erk1 and erk2 cascade neuron development decidualization positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis lung alveolus development positive regulation of macrophage differentiation blood vessel remodeling trophoblast giant cell differentiation lung vasculature development positive regulation of transcription by rna polymerase ii positive regulation of protein localization to nucleus embryo implantation negative regulation of meiotic nuclear division immune response positive regulation of cell population proliferation positive regulation of tyrosine phosphorylation of stat protein tyrosine phosphorylation of stat protein regulation of signaling receptor activity cytokine-mediated signaling pathway sources:amigo / quickgoorthologsspecieshumanmouseentrez397616878ensemblensg00000128342ensmusg00000034394uniprotp15018p09056refseq (mrna)nm_001257135nm_002309nm_001039537nm_008501refseq (protein)np_001244064np_002300np_001034626np_032527location (ucsc)chr 22: 30.24 – 30.25 mbchr 11: 4.21 – 4.22 mbpubmed searchwikidataview/edit humanview/edit mouse function lif derives its name from its ability to induce the terminal differentiation of myeloid leukemic cells, thus preventing their continued growth. other properties attributed to the cytokine include: the growth promotion and cell differentiation of different types of target cells, influence on bone metabolism, cachexia, neural development, embryogenesis and inflammation. p53 regulated lif has been shown to facilitate implantation in the mouse model and possibly in humans. it has been suggested that recombinant human lif might help to improve the implantation rate in women with unexplained infertility. binding/activation lif binds to the specific lif receptor (lifr-α) which forms a heterodimer with a specific subunit common to all members of that family of receptors, the gp130 signal transducing subunit. this leads to activation of the jak/stat (janus kinase/signal transducer and activator of transcription) and mapk (mitogen activated protein kinase) cascades. expression lif is normally expressed in the trophectoderm of the developing embryo, with its receptor lifr expressed throughout the inner cell mass. as embryonic stem cells are derived from the inner cell mass at the blastocyst stage, removing them from the inner cell mass also removes their source of lif. recombinant lif has been produced in plants by invitria. use in stem cell culture lif is often added to stem cell culture media as an alternative to feeder cell culture, due to the limitation that feeder cells present by only producing lif on their cell surfaces. feeder cells lacking the lif gene do not effectively support stem cells. lif promotes self-renewal by recruiting signal transducer and activator of transcription 3 (stat3). stat3 is recruited to the activated lif receptor and phosphorylated by janus kinase. it bears noting that lif and stat3 are not sufficient to inhibit stem cell differentiation, as cells will differentiate upon removal of serum. during the reversibility phase of differentiation from naive pluripotency, it is possible to revert cells back to naive pluripotency through the addition of lif. removal of lif pushes stem cells toward differentiation, however genetic manipulation of embryonic stem cells allows for lif independent growth, notably overexpression of the gene nanog. lif is typically added to stem cell culture medium to reduce spontaneous differentiation.