Cytokine or growth factor activated STAT3 undergoes multiple post-translational modifications, dimerization and translocation into nuclei, where it binds to serum-inducible element (SIE, 'TTC(N3)GAA')-bearing promoters to activate transcription. The STAT3 DNA binding domain (DBD, 320-494) mutation in hyper immunoglobulin E syndrome (HIES), called the HIES mutation (R382Q, R382W or V463Δ), which...

MicroRNA (miR) abnormalities play a key role in the pathogenesis of chronic lymphocytic leukemia (CLL). High levels of miR-155 have been detected in human neoplasms, and overexpression of miR-155 has been found to induce lymphoma in mice. High levels of miR-155 were detected in CLL cells and STAT3, which is known to induce miR-21 and miR-181b-1 expression, is constitutively activated in CLL. Gi...

BACKGROUND & AIMS The human hepatitis B virus (HBV) is a major cause of chronic hepatitis and hepatocellular carcinoma, but molecular mechanisms driving liver disease and carcinogenesis are largely unknown. We therefore studied cellular pathways altered by HBV infection. METHODS We performed gene expression profiling of primary human hepatocytes infected with HBV and proved the results in HBV...

Stat3 plays diverse roles in biological processes including cell proliferation, survival, apoptosis, and inflammation. Very little is known regarding its activation and function in the lung during acute inflammation. We now show that Stat3 activation was triggered in lungs and in alveolar macrophages after intrapulmonary deposition of IgG immune complexes in rats. Low levels of constitutive Sta...

Activated forms of STAT3 transcription factors are often found in various cancers and tumor cell lines, indicating that this signaling pathway is involved in tumorogenesis. At the molecular level, STAT3 proteins function as transcriptional activators and up-regulate several growth-promoting genes such as myc, pim-1, or cyclin D1. However, these transcription factors have also proapoptotic funct...

A variety of cytokines induce the tyrosine phosphorylation of signal transducers and activators of transcription (STATs). Activation of the same STAT proteins by distinct cytokines and activation of different STAT proteins by each cytokine are thought to contribute to redundancy and pleiotropy of cytokine actions respectively. STAT3 is rapidly tyrosine phosphorylated in response to IL-6, ciliar...

The atherogenic cytokine IL-6 (interleukin-6) induces pro-inflammatory gene expression in VECs (vascular endothelial cells) by activating the JAK (Janus kinase)/STAT3 (signal transducer and activator of transcription 3) signalling pathway, which is normally down-regulated by the STAT3-dependent induction of the E3 ubiquitin ligase component SOCS3 (suppressor of cytokine signalling 3). Novel tre...

Signal Transducer and Activator of Transcription 3 (STAT3) is a transcription factor that plays a crucial role in interleukin-6 (IL-6) signaling, mediating the acute-phase induction of the human Angiotensinogen (hAGT) gene in hepatocytes. We showed earlier that IL-6 induces acetylation of the STAT3 NH(2)-terminus by the recruitment of the p300 coactivator. We had also observed a physical intera...

Signal transducer and activator of transcription 3 (Stat3) is a key regulator of gene expression in response to signaling of the glycoprotein 130 (gp130) family cytokines, including interleukin 6, oncostatin M, and leukemia inhibitory factor. Many efforts have been made to identify Stat3 target genes and to understand the mechanism of how Stat3 regulates gene expression. Using the microarray te...

In a recent study, we have shown that STAT3 expressed by tumor cells blunts antitumor immunity during carcinogen-induced lung tumorigenesis. STAT3 inhibits the production of pro-inflammatory chemokines and MHC Class I chain-related gene A. In contrast, STAT3 promotes the expression of MHC class I molecules. Consequently, STAT3 promotes tumor cell resistance to NK cell-mediated cytotoxicity.