STATs: transcriptional control and biological impact
Nature Reviews Molecular Cell BiologyPublished 1 September 2002
David E. Levy, James Darnell
Citations3,191
SJR quartileQ1
SJR score37.35
SNIP20.23
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TL;DR
The signal transducer and activator of transcription proteins are among the most well studied of the latent cytoplasmic signal-dependent transcription-factor pathways, and their dysregulation contributes to human disease.
Abstract
Extracellular proteins bound to cell-surface receptors can change nuclear gene expression patterns in minutes, with far-reaching consequences for development, cell growth and homeostasis. The signal transducer and activator of transcription (STAT) proteins are among the most well studied of the latent cytoplasmic signal-dependent transcription-factor pathways. In addition to several roles in normal cell decisions, dysregulation of STAT function contributes to human disease, making the study of these proteins an important topic of current research.
Keywords
Immunology and MicrobiologyMedicineBiochemistry, Genetics and Molecular Biology
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516 Citations1997Aseem Kumar, Mairead Commane +3 more
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359 Citations1999Min You, Dehua Yu +1 more
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351 Citations2001Stephen Brown, Nan Hu +1 more
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345 Citations2000Shizuo Akira
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344 Citations2000Moitreyee Chatterjee‐Kishore, Kenneth L. Wright +2 more
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343 Citations1995Michael David, Haiyan E. Chen +3 more
It is found that SH2 domain-containing PTP1 (SHPTP1) reversibly associates with the IFN-alpha receptor complex upon IFN addition, establishing that SHPTP 1 selectively regulates distinct components of Jak/Stat signal transduction pathways in vivo.
Molecular and Cellular BiologyEssential Role of STAT3 in the Control of the Acute-Phase Response as Revealed by Inducible Gene Activation in the Liver
338 Citations2001Tonino Alonzi, Diego Maritano +4 more
Analysis of the induction of liver acute-phase genes in response to bacterial lipopolysaccharide unequivocally identifies STAT3 as a fundamental mediator of their induction.
The Journal of Experimental MedicineHuman Cytomegalovirus Inhibits Major Histocompatibility Complex Class II Expression By Disruption of the Jak/Stat Pathway
333 Citations1998Daniel M. Miller, Brian M. Rahill +5 more
It is demonstrated that both a clinical isolate and a laboratory strain of HCMV inhibit inducible MHC class II expression at the cell surface and at RNA level in human endothelial cells and fibroblasts.
OncogeneComplex roles of Stat1 in regulating gene expression
331 Citations2000Chilakamarti V. Ramana, Moitreyee Chatterjee‐Kishore +2 more
This review summarizes the well studied involvement of Stat1 in IFN-dependent and growth factor-dependent signaling and then describes the roles of Stat 1 in positive, negative and constitutive regulation of gene expression as well as its participation in crosstalk between signal transduction pathways.
Journal of VirologyHepatitis C Virus Nonstructural 5A Protein Induces Interleukin-8, Leading to Partial Inhibition of the Interferon-Induced Antiviral Response
317 Citations2001Stephen J. Polyak, Khalid S.A. Khabar +7 more
It is suggested that NS5A inhibits the antiviral actions of IFN by at least two mechanisms and the first evidence for a biological effect of the transcriptional activity of the NS5a protein is provided.
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313 Citations1995Hongbo R. Luo, William P. Hanratty +1 more
It is demonstrated that the hopTum‐l hematopoietic phenotype is caused by a single amino acid substitution of glycine to glutamic acid at residue 341, and the results indicate that a mutant Jak kinase can cause leukemia‐like abnormalities.
CellParacrine Signaling through the JAK/STAT Pathway Activates Invasive Behavior of Ovarian Epithelial Cells in Drosophila
307 Citations2001Debra L. Silver, Denise J. Montell
It is found that JAK and STAT are required to convert the border cells in the Drosophila ovary from stationary, epithelial cells to migratory, invasive cells.
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306 Citations1996Uwe Vinkemeier, Steven L. Cohen +4 more
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305 Citations1999Minghua Zhu, Susan John +2 more
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304 Citations1995Andrew C. Greenlund, Mary O. Morales +4 more
The results demonstrate that IFN gamma-induced Stat1 activation is an ordered and affinity-driven process and it is proposed that this process may serve as a paradigm for Stat activation by other cytokine receptors.
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302 Citations2001Andrew W. Roberts, Lorraine Robb +7 more
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290 Citations1999Robyn Starr, Douglas J. Hilton
The duration and intensity of a cell's response to cytokine appears to be determined by the net effect of several regulatory mechanisms, including receptor/ligand complex, JAK kinases, and STAT transcription factors.
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284 Citations2002Kevin M. McBride, Gregg Banninger +2 more
A direct interaction of importin‐α5 with tyrosine‐phosphorylated STAT1 dimers is demonstrated, and evidence that a nuclear localization signal (NLS) exists in an inactive state within a STAT1 monomer is provided, and it is demonstrated that STAT1 binding to specific target DNA effectively blocks importin-α5 binding.
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270 Citations1998Uwe Vinkemeier, Ismail Moarefi +2 more
The crystal structure of an NH2-terminal conserved domain (N-domain) comprising the first 123 residues of STAT-4 was determined and shows that N-domains can interact through an extensive interface formed by polar interactions across one face of the hook.
Journal of Biological ChemistryStat1 Depends on Transcriptional Synergy with Sp1
269 Citations1995Dwight C. Look, Mark Pelletier +3 more
Assays of DNA/protein binding and activity of transfected reporter plasmids determined that occupation of contiguous DNA-binding sites for Stat1 (the first member of the STAT family) and the transcriptional activator Sp1 are both required for full activation of the intercellular adhesion molecule-1 gene by interferon - thus, Stat1 binding to DNA cannot by itself be equated with biologic actions of Stat1.
Proceedings of the National Academy of SciencesLigand-independent oligomerization of cell-surface erythropoietin receptor is mediated by the transmembrane domain
266 Citations2001Stefan N. Constantinescu, Tzvia Keren +4 more
A model in which TM domain-induced dimerization maintains unliganded EpoR in an inactive state that can readily be switched to an active state by physiologic levels of Epo is proposed.
Molecular CellVesicular Stomatitis Virus Matrix Protein Inhibits Host Cell Gene Expression by Targeting the Nucleoporin Nup98
263 Citations2000Cayetano von Kobbe, Jan M. A. van Deursen +7 more
It is demonstrated that VSV M inhibits host cell gene expression by targeting a nucleoporin and primarily blocking nuclear export.
The Journal of ImmunologyMultilevel Dysregulation of STAT3 Activation in Anaplastic Lymphoma Kinase-Positive T/Null-Cell Lymphoma
261 Citations2002Qian Zhang, Puthryaveett N. Raghunath +7 more
It is reported that NPM/ALK induces continuous activation of STAT3 and that PP2A and lack of protein inhibitor of activated STAT3 may be important in maintaining STAT3 in the activated state in the ALK+ TCL cells.
Molecular and Cellular BiologyPlatelet-Derived Growth Factor Induces Phosphorylation of Multiple JAK Family Kinases and STAT Proteins
244 Citations1996Marie‐Luce Vignais, Henry B. Sadowski +3 more
All three of the ubiquitously expressed JAKs--JAK1, JAK2, and Tyk2--become phosphorylated on tyrosine in both mouse BALB/c 3T3 cells and human fibroblasts engineered to express the PDGF-beta receptor, suggesting that the mechanism of JAK activation and JAK function in signaling differs between receptor tyrosines kinases and interferon receptors.
ImmunitySTAT3 Is a Negative Regulator of Granulopoiesis but Is Not Required for G-CSF-Dependent Differentiation
243 Citations2002Chien‐Kuo Lee, Regina Raz +6 more
These studies provide direct evidence for STAT3-independent granulopoiesis and suggest that STAT3 directs a negative feedback loop necessary for controlling neutrophil numbers, possibly through induced expression of the signaling inhibitor, SOCS3.
Genes & DevelopmentA new RING for SUMO: wrestling transcriptional responses into nuclear bodies with PIAS family E3 SUMO ligases
243 Citations2001Peter K. Jackson
The Journal of ImmunologySuppressors of Cytokine Signaling Proteins Are Differentially Expressed in Th1 and Th2 Cells: Implications for Th Cell Lineage Commitment and Maintenance
240 Citations2002Charles E. Egwuagu, Cheng‐Rong Yu +4 more
It is shown that CD4+ naive T cells constitutively express low levels of SOCS1, SOCS2, and SOCS3 mRNAs, and that differentiation into Th1 or Th2 phenotype is accompanied by preferential expression of distinct SOCS mRNA transcripts and proteins, suggesting mutually exclusive use of STAT4 and STAT6 signaling pathways by differentiated Th cells.
OncogeneJAKs, STATs and Src kinases in hematopoiesis
238 Citations2002Sushil G. Rane, E. Premkumar Reddy
Cell and tissue-specificity of cytokine action appears to be determined by the nature of signal transduction pathways activated by cytokine/receptor interactions, and the integration of these diverse signaling cues from active JAK kinases, members of the Src-family kinases and STAT proteins, leads to cell proliferation, cell survival and differentiation, the end-point of the cytokin/growth factor stimulus.
Journal of Biological ChemistrySTAT3 Acts as a Co-activator of Glucocorticoid Receptor Signaling
238 Citations1997Zhixin Zhang, Simon A. Jones +3 more
These findings reveal a new level of interaction between these two crucial signaling cascades and indicate that activated STAT3 can also act as a transcriptional co-activator without direct association with its DNA binding motif.
Journal of Biological ChemistryStat Protein Transactivation Domains Recruit p300/CBP through Widely Divergent Sequences
235 Citations1999Matthew Paulson, Sobha Pisharody +4 more
Cloned mouse Stat2 was cloned and found that while its sequence was more divergent from its human homologue than any other mouse-human Stat pairs, it was fully functional even in human cells, demonstrating that highly diverged primary sequences can serve similar or identical functions.
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