STAT3

STAT3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 5AX3
Identifiers
Aliases	STAT3, ADMIO, APRF, HIES, signal transducer and activator of transcription 3, ADMIO1
External IDs	OMIM: 102582 MGI: 103038 HomoloGene: 7960 GeneCards: STAT3
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17q21.2 Start 42,313,324 bp[1] End 42,388,568 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11 D|11 63.82 cM Start 100,775,924 bp[2] End 100,830,366 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in pericardium lower lobe of lung lactiferous duct nipple right ventricle upper lobe of lung upper lobe of left lung vena cava trachea spinal ganglia Top expressed in right lung lobe ankle left lung epithelium of stomach ankle joint left lung lobe uterus lip submandibular gland median eminence More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein dimerization activity DNA-binding transcription factor activity DNA-binding transcription activator activity, RNA polymerase II-specific nuclear receptor activity protein phosphatase binding RNA polymerase II cis-regulatory region sequence-specific DNA binding protein binding protein kinase binding DNA binding sequence-specific DNA binding chromatin DNA binding protein homodimerization activity identical protein binding DNA-binding transcription factor activity, RNA polymerase II-specific signal transducer activity transcription factor binding CCR5 chemokine receptor binding glucocorticoid receptor binding Cellular component cytoplasm mitochondrion nucleus plasma membrane nucleoplasm RNA polymerase II transcription regulator complex mitochondrial inner membrane cytosol postsynaptic density Schaffer collateral - CA1 synapse glutamatergic synapse transcription regulator complex Biological process negative regulation of glycolytic process protein import into nucleus regulation of transcription by RNA polymerase II transcription by RNA polymerase II response to organic substance positive regulation of gene silencing by miRNA radial glial cell differentiation stem cell population maintenance cellular response to hormone stimulus regulation of mitochondrial membrane permeability growth hormone receptor signaling pathway miRNA-mediated gene silencing by inhibition of translation eye photoreceptor cell differentiation positive regulation of metalloendopeptidase activity temperature homeostasis cell population proliferation response to leptin response to ethanol positive regulation of Notch signaling pathway negative regulation of cell population proliferation response to cytokine regulation of transcription, DNA-templated glucose homeostasis negative regulation of cell death transcription, DNA-templated positive regulation of growth factor dependent skeletal muscle satellite cell proliferation positive regulation of transcription, DNA-templated negative regulation of hydrogen peroxide biosynthetic process energy homeostasis viral process negative regulation of neuron death sexual reproduction phosphorylation leptin-mediated signaling pathway cellular response to organic cyclic compound negative regulation of apoptotic process negative regulation of transcription by RNA polymerase II regulation of feeding behavior nervous system development positive regulation of ATP biosynthetic process intracellular receptor signaling pathway acute-phase response negative regulation of neuron migration receptor signaling pathway via JAK-STAT response to estradiol response to organic cyclic compound eating behavior somatic stem cell population maintenance regulation of multicellular organism growth human ageing response to peptide hormone cellular response to leptin stimulus regulation of cell cycle astrocyte differentiation signal transduction positive regulation of transcription by RNA polymerase II growth hormone receptor signaling pathway via JAK-STAT positive regulation of gene expression negative regulation of stem cell differentiation positive regulation of cell population proliferation mRNA transcription by RNA polymerase II inflammatory response positive regulation of erythrocyte differentiation T-helper 17 cell lineage commitment positive regulation of pri-miRNA transcription by RNA polymerase II positive regulation of tyrosine phosphorylation of STAT protein interleukin-15-mediated signaling pathway interleukin-7-mediated signaling pathway positive regulation of angiogenesis positive regulation of vascular endothelial cell proliferation cytokine-mediated signaling pathway interleukin-21-mediated signaling pathway interleukin-23-mediated signaling pathway interleukin-6-mediated signaling pathway interleukin-27-mediated signaling pathway interleukin-35-mediated signaling pathway cellular response to cytokine stimulus interleukin-9-mediated signaling pathway modulation of chemical synaptic transmission postsynapse to nucleus signaling pathway negative regulation of autophagy positive regulation of cell migration positive regulation of NF-kappaB transcription factor activity defense response regulation of cell population proliferation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6774 20848 Ensembl ENSG00000168610 ENSMUSG00000004040 UniProt P40763 P42227 RefSeq (mRNA) NM_003150 NM_139276 NM_213662 NM_001369512 NM_001369513 NM_001369514 NM_001369516 NM_001369517 NM_001369518 NM_001369519 NM_001369520 NM_011486 NM_213659 NM_213660 RefSeq (protein) NP_003141 NP_644805 NP_998827 NP_001356441 NP_001356442 NP_001356443 NP_001356445 NP_001356446 NP_001356447 NP_001356448 NP_001356449 NP_035616 NP_998824 NP_998825 Location (UCSC) Chr 17: 42.31 – 42.39 Mb Chr 11: 100.78 – 100.83 Mb PubMed search [3] [4]
Wikidata
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Signal transducer and activator of transcription 3 (STAT3) is a transcription factor which in humans is encoded by the STAT3 gene.^[5] It is a member of the STAT protein family.

Function

STAT3 is a member of the STAT protein family. In response to cytokines and growth factors, STAT3 is phosphorylated by receptor-associated Janus kinases (JAK), forms homo- or heterodimers, and translocates to the cell nucleus where it acts as a transcription activator. Specifically, STAT3 becomes activated after phosphorylation of tyrosine 705 in response to such ligands as interferons, epidermal growth factor (EGF), interleukin (IL-)5 and IL-6. Additionally, activation of STAT3 may occur via phosphorylation of serine 727 by mitogen-activated protein kinases (MAPK)^[6] and through c-src non-receptor tyrosine kinase.^[7][8] STAT3 mediates the expression of a variety of genes in response to cell stimuli, and thus plays a key role in many cellular processes such as cell growth and apoptosis.^[9]

STAT3-deficient mouse embryos cannot develop beyond embryonic day 7, when gastrulation begins.^[10] It appears that at these early stages of development, STAT3 activation is required for self-renewal of embryonic stem cells (ESCs). Indeed, LIF, which is supplied to murine ESC cultures to maintain their undifferentiated state, can be omitted if STAT3 is activated through some other means.^[11]

STAT3 is essential for the differentiation of the TH17 helper T cells, which have been implicated in a variety of autoimmune diseases.^[12] During viral infection, mice lacking STAT3 in T-cells display impairment in the ability to generate T-follicular helper (Tfh) cells and fail to maintain antibody based immunity.^[13]

STAT3 caused upregulation in E-selectin, a factor in metastasis of cancers.^[14]

Hyperactivation of STAT3 occurs in COVID-19 infection and other viral infections.^[15][16]

Clinical significance

Loss-of-function mutations in the STAT3 gene result in hyperimmunoglobulin E syndrome, associated with recurrent infections as well as disordered bone and tooth development.^[17]

Gain-of-function mutations in the STAT3 gene have been reported to cause multi-organ early onset auto-immune diseases; such as thyroid disease, diabetes, intestinal inflammation, and low blood counts,^[18] while constitutive STAT3 activation is associated with various human cancers and commonly suggests poor prognosis.^{[19][20][21][22]} It has anti-apoptotic as well as proliferative effects.^[19]

STAT3 can promote oncogenesis by being constitutively active through various pathways as mentioned elsewhere. A tumor suppressor role of STAT3 has also been reported.^[23][24][25] In the report on human glioblastoma tumor, or brain cancer, STAT3 was shown to have an oncogenic or a tumor suppressor role depending upon the mutational background of the tumor. A direct connection between the PTEN-Akt-FOXO axis (suppressive) and the leukemia inhibitory factor receptor beta (LIFRbeta)-STAT3 signaling pathway (oncogenic) was shown.

Increased activity of STAT3 in cancer cells, leads to changes in the function of protein complexes that control expression of inflammatory genes, with result profound change in the secretome and the cell phenotypes, their activity in the tumor, and their capacity for metastasis.^[26]

Interactions

STAT3 has been shown to interact with:

Niclosamide seems to inhibit the STAT3 signalling pathway.^[56]

Nicotinamide (a type of vitamin B₃) naturally inhibits STAT3.^[57] However NAC (Acetylcysteine) inhibits STAT3 inhibitors.^[58]

References

Further reading

External links

• FactorBook STAT3