Drug Target and Biomarker: STAT3 (G6774)

NCBI ID: G6774

STAT3

Drug Target and Biomarker: STAT3

STAT3 is a signaling protein involved in the regulation of gene transcription. It is activated by phosphorylation and forms dimers that translocate into the nucleus to activate target genes.
miRNAs play a critical role in regulating STAT3 in various types of human cancers.
The inhibition of the STAT3 signaling pathway can lead to the inhibition of tumor growth, invasion, and induction of cancer cell apoptosis.
Notch pathway and inflammatory elements interact with STAT3 to promote breast cancer progression.
IL-18 can influence colitis by regulating the function of goblet cells through the IL-22/STAT3 signaling pathway.
DNA methylation, regulated by inflammatory cytokines, can affect the transformation of inflammation into colorectal cancer by modulating STAT3/NF-kappaB signaling.

Overall, STAT3 is a key factor in cancer progression, and its regulation and interactions with other proteins and pathways play a crucial role in various cancer types.
STAT3, also known as mitoSTAT3, plays a critical role in various cellular processes and signaling pathways. Upon initial stimulation, mitoSTAT3 undergoes posttranslational modifications, leading to its association with mitochondrial proteases and subsequent proteolytic cleavage. Proteolytic fragments of mitoSTAT3 may potentially contribute to extramitochondrial signaling.

Further research reveals that the activation of STAT3 promotes the transcription of miR-384 and Rorgammat (RORC), which are involved in Th17 cell polarization. Additionally, SUMOylation and SENP3 are implicated in the regulation of STAT3 activation, particularly in basal and stressed microenvironments affected by cigarette components and excessive IL-6.

In the context of cancer immunity, STAT3 phosphorylation in cancer cells facilitates interactions between immune cells in the tumor microenvironment, promoting tumor growth, angiogenesis, and metastasis. STAT3 also regulates the expression of immune checkpoint molecule PD-L1, which has downstream effects on immune checkpoint regulation.

Moreover, a new protein loop involving STAT3/SHMT2/PKM2, rather than the previously known STAT3/HIF-1alpha/PKM2 loop, can be active under inflammatory conditions. This alternate loop contributes to metabolic shifts and oxidative stress, ultimately leading to stabilized anaerobic glycolysis.

In summary, STAT3 is involved in various cellular processes such as mitochondrial stability, Th17 cell polarization, regulation of immune checkpoints, and metabolic shifts under inflammatory conditions. Its activation and modulation play pivotal roles in both normal cellular functions and pathological processes such as cancer.

Protein Name: Signal Transducer And Activator Of Transcription 3

Functions: Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:10688651, PubMed:12359225, PubMed:12873986, PubMed:15194700, PubMed:17344214, PubMed:18242580, PubMed:22306293, PubMed:23084476). Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene (PubMed:17344214). May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4 (PubMed:12873986). Upon activation of IL6ST/gp130 signaling by interleukin-6 (IL6), binds to the IL6-responsive elements identified in the promoters of various acute-phase protein genes (PubMed:12359225). Activated by IL31 through IL31RA (PubMed:15194700). Acts as a regulator of inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg): deacetylation and oxidation of lysine residues by LOXL3, leads to disrupt STAT3 dimerization and inhibit its transcription activity (PubMed:28065600). Involved in cell cycle regulation by inducing the expression of key genes for the progression from G1 to S phase, such as CCND1 (PubMed:17344214). Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation (By similarity). May play an apoptotic role by transctivating BIRC5 expression under LEP activation (PubMed:18242580). Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity (PubMed:23084476). Plays a crucial role in basal beta cell functions, such as regulation of insulin secretion (By similarity)

The "STAT3 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 STAT3 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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