Leukemia inhibitory factor

Leukemia inhibitory factor
PDB rendering based on 1LKI.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1EMR, 1PVH, 2Q7N
Identifiers
Symbols	LIF ; CDF; DIA; HILDA; MLPLI
External IDs	OMIM: 159540 MGI: 96787 HomoloGene: 1734 GeneCards: LIF Gene
Gene ontology Molecular function • transcription factor activity, RNA polymerase II transcription factor recruiting • receptor binding • cytokine activity • leukemia inhibitory factor receptor binding • growth factor activity Cellular component • extracellular space • cytoplasm Biological process • blood vessel remodeling • immune response • multicellular organismal development • embryo implantation • positive regulation of cell proliferation • negative regulation of cell proliferation • positive regulation of neuron projection development • negative regulation of angiogenesis • stem cell maintenance • organ regeneration • 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 meiotic nuclear division • positive regulation of transcription from RNA polymerase II promoter • decidualization • negative regulation of hormone secretion • lung alveolus development • muscle organ morphogenesis • neuron development • astrocyte differentiation • positive regulation of astrocyte differentiation • leukemia inhibitory factor signaling pathway • positive regulation of peptidyl-tyrosine phosphorylation • positive regulation of corticotropin secretion • retina development in camera-type eye • transdifferentiation • 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 • regulation of RNA polymerase II regulatory region sequence-specific DNA binding Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3976	16878
Ensembl	ENSG00000128342	ENSMUSG00000034394
UniProt	P15018	P09056
RefSeq (mRNA)	NM_001257135	NM_001039537
RefSeq (protein)	NP_001244064	NP_001034626
Location (UCSC)	Chr 22: 30.24 – 30.25 Mb	Chr 11: 4.26 – 4.27 Mb
PubMed search	[1]	[2]

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.

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.

Use in stem cell culture

Removal of LIF pushes stem cells toward differentiation, but they retain their proliferative potential or pluripotency. Therefore LIF is used in mouse embryonic stem cell culture. It is necessary to maintain the stem cells in an undifferentiated state, 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.

External links

• Leukemia Inhibitory Factor at the US National Library of Medicine Medical Subject Headings (MeSH)
• Source of Recombiant Leukemia Inhibitory Factor (http://www.invitria.com/cell-culture-products-services/leukemia-inhibitory-factor-culture-media.html )