Drug Target and Biomarker: STAT1 (G6772)

NCBI ID: G6772

STAT1

Drug Target and Biomarker: STAT1

Protein expression changes in vSCC tumors: Increased expression of STAT1 and proteasome proteins in vSCC tumors with a pushing morphology leads to activation of a signaling pathway associated with a lymphoplasmacytic stromal response, inhibiting tumor growth and aggressive behavior. In contrast, tumors with an infiltrative morphology have increased collagen expression and activation of integrin signaling, promoting tumor growth and aggressive behavior.

Interaction of STAT1beta with STAT1alpha: STAT1 can form different dimers, including alpha:alpha homodimers, beta:beta homodimers, and alpha:beta heterodimers. STAT1beta can bind to STAT1alpha to protect it from degradation, resulting in prolonged half-life of STAT1alpha and increased transcription activity.

IFN-gamma signaling and STAT1 involvement: IFN-gamma primes enhancers and promoters via recruitment of STAT1 and interferon regulatory factor 1 (IRF1), leading to increased histone acetylation and chromatin remodeling. IFN-gamma also induces the formation of latent enhancers by inducing transcription factors that cooperate with other proteins to form new enhancers.

HCMV-mediated suppression of type I interferon response: HCMV infection disrupts STAT1 phosphorylation and nuclear localization, inhibiting type I interferon signaling. This prevents the transcriptional activation of interferon-stimulated genes (ISGs) and facilitates viral immune escape from type I interferon.

ISG regulation by STAT1 and STAT2 in cancer cells: In BCR-ABL-expressing cells, STAT2 is partially phosphorylated, leading to ISG repression and lack of STAT1 induction. In JAK2V617F-positive cells, STAT2 can induce STAT1 expression and is essential for STAT1 phosphorylation upon IFN-alpha stimulation. The equilibrium of STAT1/STAT1 and STAT1/STAT3 dimers also varies depending on the amount of active STAT2.

These key viewpoints present various aspects of STAT1 function and its involvement in different biological processes, such as tumor behavior, dimer formation, IFN-gamma signaling, viral immune evasion, and regulation of ISGs in cancer cells.

The expression of STAT1 and UBC in LUAD tissue is significantly lower than in control tissue, and high expression of UBC and STAT1 can inhibit the development of LUAD.

During DENV infection, the phosphorylation of STAT1 is reduced, resulting in less viral progeny production. However, in DENV-antibody-dependent enhancement (ADE) infection, STAT1 phosphorylation is attenuated, leading to increased viral progeny production.

Hypoxia downregulates the type I IFN pathway, and it is independent of HIF1alpha. This mechanism involves the downregulation of STAT1.

Mutating certain amino acids (Lys511 and Lys652) in STAT1 enhances the IFN-I response in vivo, including STAT1-Tyr701 phosphorylation and ISG expression.

PI3K signaling can repress the expression of MHC molecules and their induction by IFN-gamma, potentially through attenuating STAT1 protein levels and phosphorylation. Inhibiting PI3K or loss of PIK3CA can diminish the repressive effects and increase MHC expression, promoting CD4+ and/or CD8+ T-cell activation and anti-tumor immunity.

Protein Name: Signal Transducer And Activator Of Transcription 1

Functions: Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors (PubMed:34508746, PubMed:35568036). Following type I IFN (IFN-alpha and IFN-beta) binding to cell surface receptors, signaling via protein kinases leads to activation of Jak kinases (TYK2 and JAK1) and to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize and associate with ISGF3G/IRF-9 to form a complex termed ISGF3 transcription factor, that enters the nucleus (PubMed:28753426, PubMed:35568036). ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of IFN-stimulated genes (ISG), which drive the cell in an antiviral state. In response to type II IFN (IFN-gamma), STAT1 is tyrosine- and serine-phosphorylated (PubMed:26479788). It then forms a homodimer termed IFN-gamma-activated factor (GAF), migrates into the nucleus and binds to the IFN gamma activated sequence (GAS) to drive the expression of the target genes, inducing a cellular antiviral state. Becomes activated in response to KITLG/SCF and KIT signaling. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4

The "STAT1 Target / Biomarker Review Report" is a customizable review of hundreds up to thousends of related scientific research literature by AI technology, covering specific information about STAT1 comprehensively, including but not limited to:
•   general information;
•   protein structure and compound binding;
•   protein biological mechanisms;
•   its importance;
•   the target screening and validation;
•   expression level;
•   disease relevance;
•   drug resistance;
•   related combination drugs;
•   pharmacochemistry experiments;
•   related patent analysis;
•   advantages and risks of development, etc.
The report is helpful for project application, drug molecule design, research progress updates, publication of research papers, patent applications, etc. If you are interested to get a full version of this report, please feel free to contact us at BD@silexon.ai

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