Summary of STAT3
STAT3 is a protein that binds to DNA and increases expression of certain immune genes that can cause inflammation that leads to autoimmunity, but also fight infections. The STAT3 pathway is used by a variety of cytokines, hormones and growth factors to increase blood cell formation, immune cell development, stem cell maintenance, and growth. However, chronic activation of STAT3 underlies various diseases or disorders, such as cancer or obesity (R).
Read: Natural STAT3 Inhibitors
The STAT3 gene is part of a family known as the STAT genes. These genes provide instructions for making proteins that are part of essential chemical signaling pathways within cells. When STAT proteins are activated by certain chemical signals, they move into the nucleus and attach (bind) to specific areas of DNA. By binding to regulatory regions near genes, STAT proteins can regulate whether these genes are turned on or off. STAT proteins are called transcription factors on the basis of this action. The STAT3 protein is involved in many cellular functions. It regulates genes that are involved in cell growth and division, cell movement, and the self-destruction of cells (apoptosis). The STAT3 protein is active in tissues throughout the body. It plays an important role in the development and function of several body systems and is essential for life. In the immune system, the STAT3 protein transmits signals for the maturation of immune system cells, especially T cells and B cells. These cells help control the body's response to foreign invaders such as bacteria and fungi. In addition, the protein is involved in the regulation of inflammation, which is one way the immune system responds to infection or injury. In the skeletal system, the STAT3 protein is involved in the formation of specialized cells that build and break down bone tissue. These cells are necessary for the normal development and maintenance of bones.
STAT3 (Good):
- helps with insulin sensitivity (R).
- when chronically elevated will cause obesity (R).
- suppresses of glucose production (R).
- helps with liver regeneration (R).
- helps reduce fatty liver disease (R).
- has some anti-cancer properties, especially for CML (R).
- helps clear pathogens (R).
- suppresses IgE responses (R).
STAT3 (Bad):
- STAT3 contributes to the development of IBD (R).
- can help cause multiple sclerosis (MS)(R).
- creates Th1 and Th17 cells (R), which are immune cells involved in autoimmunity.
- produces pro-cancer products such as MMP-3, MMP-9, VEGF, HIF-1a, COX2, IL-6, IL-23 and ICAM1 (R).
Protein names
Recommended name:
Signal transducer and activator of transcription 3Alternative name(s):
Acute-phase response factor- RS12942547 (STAT3) ??
- RS17881320 (STAT3) ??
- RS2293152 (STAT3) ??
- RS4796793 (STAT3) ??
- RS6503691 (STAT3) ??
- RS6503695 (STAT3) ??
- RS744166 (STAT3) ??
- RS8069645 (STAT3) ??
- RS9891119 (STAT3) ??
To see your genotype, you should be logged in and have a file with your genotype uploaded.
Top Gene-Substance Interactions
STAT3 Interacts with These Diseases
| Disease | Score |
Fixes
Natural STAT3 Inhibitors
- Spices/²-Caryophyllene oxide (in black pepper, cinnamon, clove, lemon balm, oregano, cannabis, rosemary, hops),
- Fish oil (R),
- Silibinin (R) - Milk Thistle
- Bilberry (R),
- Black Cumin Seed Oil / Thymoquinone (R),
- Olive oil (extra virgin) (R),
- Zinc (R) (constitutive=always active),
- Lithium (R) (constitutive),
- EGCG (R) (constitutive),
- Curcumin (R) (constitutive),
- Broccoli sprouts/Cruciferous veggies/Sulforaphane (R),
- Cayenne/Capsaicin (R)
Fixes Advanced
Other Supplements to Inhibit STAT3:
- Resveratrol
(R) (constitutive),
- Quercetin (R),
- Luteolin (R) (constitutive),
- Apigenin
(R) (constitutive),
- Grape Seed Extract (R)
- Ursolic acid (R) (constitutive),
- Bile (R),
- Boswellia/Boswellic Acid (R),
- Cayenne/Capsaicin (R) - in peppers,
- Gynostemma/H6 (R),
- Emodin (Resveratrol
- Berberine (R)
- Epimedium/Icariin (R),
- Bitter melon (Cucurbitacin E) (R),
- Guggul/Guggulsterone (R) (constitutive),
- Parthenolide/Feverfew (R),
- CognI-Q/Decursin,
- Others: Caffeic acid, Betulinic acid(chaga), Morin (guava leaf), Plumbagin(black walnut hull), Diosmin (R), Garcinol (R) (constitutive), Celastrol, Gambogic acid, Butein, Auranofin(prescription),
Beware of STAT3 Activators
Substances That Increase STAT3
| Substances | Interaction | Organism | Category |
Substances That Decrease STAT3
| Substances | Interaction | Organism | Category |
Advanced Summary
The Benefits of STAT3
Mice with defective or less STAT3 develop insulin resistance (R). Mice with disruption of neural STAT3 causes obesity, diabetes, infertility, and thermal dysregulation (R).
STAT3 in the liver contributes to the brain insulin action leading to the suppression of glucose production (R). STAT3 is able to activate several pathways related to liver regeneration and acute inflammatory reaction after liver injury (R).
Less STAT3 can contribute to fatty liver disease, and STAT3 gene variants are associated with it (R). STAT3 has some anti-cancer properties. In particular, it's needed for the anti-tumor effects of interferon alpha in Chronic Myelogenous Leukemia (CML) (R).
In obesity, chronic STAT3 is activated in the brain by increased leptin levels leading to the development of leptin resistance, whereas in the peripheral organs chronic IL-6-induced JAK-STAT3 impairs insulin action.
We report the consequences of chronic JAK-STAT3 induced signaling as present under obese conditions in the main metabolic organs. (R) Cells/tissues without STAT3 shows impaired pathogen response (R). When cells completely lose STAT3 function people can develop excess IgE responses (R).
Mice lacking STAT3 specifically in the liver have insulin resistance and glucose intolerance when fed a high-fat diet and restoration of STAT3 expression in these mice corrected the abnormalities (R).
STAT3 plays an important role in the induction of liver acute-phase genes in response to bacterial LPS (R).
STAT3 action in the mouse hypothalamus and liver appears essential for normal body weight and glucose homeostasis in response to the actions of both leptin and insulin (R).
The Negatives of STAT3
STAT3 contributes to the development of IBD in mice and genetic studies (R). Mice without STAT3 in T cells are resistant to animal models of multiple sclerosis (MS)(R)
. Specifically, inhibiting STAT3 will inhibit Th1 and Th17 cells (R), which are immune cells involved in autoimmunity. All in all, STAT3 plays an important role in autoimmune and inflammatory diseases and some cancers.
STAT3 produces pro-cancer products such as MMP-3, MMP-9, VEGF, HIF-1a, COX2, IL-6, IL-23 and ICAM1 (R).
The Thin/Inflammation Phenotype vs The Obese Standard American
STAT3 is another one of those proteins which if inhibited or if it's not working right will cause insulin and leptin resistance and obesity . On the other hand, if it's overactive, it will cause autoimmune conditions, inflammation, and cancer. So STAT3 has good and bad properties. You can look at your genes at the end.
Conditions with Increased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
|---|
Conditions with Decreased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
|---|
Technical
The following transcription factors affect gene expression:
Tissue specificity:
Heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.
Gene Pathways:
Molecular Function:
- Rna Polymerase Ii Core Promoter Proximal Region Sequence-Specific Dna Binding
- Transcriptional Activator Activity, Rna Polymerase Ii Core Promoter Proximal Region Sequence-Specific Binding
- Rna Polymerase Ii Repressing Transcription Factor Binding
- Transcriptional Activator Activity, Rna Polymerase Ii Transcription Regulatory Region Sequence-Specific Binding
- Dna Binding
- Transcription Factor Activity, Sequence-Specific Dna Binding
- Signal Transducer Activity
- Rna Polymerase Ii Transcription Factor Activity, Ligand-Activated Sequence-Specific Dna Binding
- Transcription Factor Binding
- Protein Kinase Binding
- Protein Phosphatase Binding
- Chromatin Dna Binding
- Identical Protein Binding
- Transcription Regulatory Region Dna Binding
- Protein Dimerization Activity
Biological Processes:
- Negative Regulation Of Transcription From Rna Polymerase Ii Promoter
- Temperature Homeostasis
- Eye Photoreceptor Cell Differentiation
- Regulation Of Transcription, Dna-Templated
- Regulation Of Transcription From Rna Polymerase Ii Promoter
- Protein Import Into Nucleus
- Movement Of Cell Or Subcellular Component
- Acute-Phase Response
- Signal Transduction
- Jak-Stat Cascade
- Nervous System Development
- Aging
- Cell Proliferation
- Positive Regulation Of Cell Proliferation
- Negative Regulation Of Cell Proliferation
- Positive Regulation Of Gene Expression
- Negative Regulation Of Hydrogen Peroxide Biosynthetic Process
- Viral Process
- Phosphorylation
- Cytokine-Mediated Signaling Pathway
- Sexual Reproduction
- Intracellular Receptor Signaling Pathway
- Response To Estradiol
- Cellular Response To Hormone Stimulus
- Leptin-Mediated Signaling Pathway
- Somatic Stem Cell Population Maintenance
- Mirna Mediated Inhibition Of Translation
- Regulation Of Multicellular Organism Growth
- Positive Regulation Of Tyrosine Phosphorylation Of Stat3 Protein
- Glucose Homeostasis
- Eating Behavior
- Mrna Transcription From Rna Polymerase Ii Promoter
- Negative Regulation Of Apoptotic Process
- Cellular Response To Leptin Stimulus
- Response To Leptin
- Response To Ethanol
- Positive Regulation Of Notch Signaling Pathway
- Negative Regulation Of Glycolytic Process
- Positive Regulation Of Transcription, Dna-Templated
- Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
- Regulation Of Mitochondrial Membrane Permeability
- Astrocyte Differentiation
- Regulation Of Cell Cycle
- Radial Glial Cell Differentiation
- Regulation Of Feeding Behavior
- Growth Hormone Receptor Signaling Pathway
- Jak-Stat Cascade Involved In Growth Hormone Signaling Pathway
- Interleukin-6-Mediated Signaling Pathway
- Cellular Response To Organic Cyclic Compound
- Energy Homeostasis
- Negative Regulation Of Neuron Death
- Positive Regulation Of Growth Factor Dependent Skeletal Muscle Satellite Cell Proliferation
- Positive Regulation Of Pri-Mirna Transcription From Rna Polymerase Ii Promoter
- Positive Regulation Of Metalloendopeptidase Activity
- Positive Regulation Of Gene Silencing By Mirna
- Negative Regulation Of Stem Cell Differentiation
- Positive Regulation Of Atp Biosynthetic Process
- Negative Regulation Of Neuron Migration