The transcription factor STAT1 plays a central role in orchestrating responses to various pathogens by activating the transcription of nuclear-encoded genes that mediate the antiviral, the antigrowth, and immune surveillance effects of interferons and other cytokines. In addition to regulating gene expression, we report that STAT1-/- mice display increased energy expenditure and paradoxically d...

BACKGROUND Signal transducer and activator of transcription 1 (Stat1) potently regulates gene expression after stimulation by certain cytokines involved in tumorigenesis and host defenses. The present study investigated a novel role for Stat1 in foam cell formation and atherosclerosis. METHODS AND RESULTS Inhibition of Stat1 activity by a Stat1-specific DNA "decoy" oligomer transfected into d...

Selective targeting of non-T cells, including antigen-presenting cells (APCs), is a potential strategy to prevent graft-versus-host-disease (GVHD) but to maintain graft-versus-tumor (GVT) effects. Because type I and II interferons signal through signal transducer and activator of transcription-1 (STAT1), and contribute to activation of APCs after allogeneic bone marrow transplant (alloBMT), we ...

Signal transducer and activator of transcription 1 (Stat1) is considered a key transcription factor that inhibits tumorigenesis, and Stat1 activation in the host is required for interleukin-12 (IL-12)-mediated generation of CTL activity. Using syngeneic Stat1-/- C3H mice bearing SCCVII tumors in this study, we discovered opposite results. Stat1 deficiency in the host significantly enhances IL-1...

Cytokines regulate viral gene expression with important consequences for viral replication and pathogenesis. Gamma interferon (IFN-gamma) is a key regulator of chronic murine gammaherpesvirus 68 (gammaHV68) infection and a potent inhibitor of gammaHV68 reactivation from latency. Macrophages are the cell type that is responsive to the IFN-gamma-mediated control of gammaHV68 reactivation; however...

The high-affinity receptor for IgG (FcgammaRI) is a myeloid cell-specific and IFN-gamma-induced gene, and thereby serves as a paradigm for cytokine-induced cell type-specific gene responses. The expression of FcgammaRI is regulated by PU.1 and Stat1 transcription factors. We established an experimental model to analyze the individual functions of Stat1 and PU.1 in cytokine-induced transcription...

Given the association with autoimmune disease, there is great interest in defining cellular factors that limit overactive or misdirected Th17-type inflammation. Using in vivo and in vitro models, we investigated the molecular mechanisms for cytokine-mediated inhibition of Th17 responses, focusing on the role of STAT1 and T-bet in this process. These studies demonstrate that, during systemic inf...

Activated tumor necrosis factor alpha (TNF-a) receptor 1 (TNFR1) recruits TNFR1-associated death domain protein (TRADD), which in turn triggers two opposite signaling pathways leading to caspase activation for apoptosis induction and NF-kB activation for antiapoptosis gene upregulation. Here we show that Stat1 is involved in the TNFR1-TRADD signaling complex, as determined by employing a novel ...

Previous studies had implicated the IFN-γ transcription factor signal transducer and activator of transcription 1 (STAT1) as a tumor suppressor. However, accumulating evidence has correlated increased STAT1 activation with increased tumor progression in multiple types of cancer, including breast cancer. Indeed, we present evidence that tumor up-regulation of STAT1 activity in human and mouse ma...

BACKGROUND The Signal Transducer and Activator of Transcription 1 (STAT1) has traditionally been regarded as a transmitter of interferon signaling and a pro-apoptotic tumour suppressor. Recent data have identified new functions of STAT1 associated with tumourigenesis and resistance to genotoxic stress, including ionizing radiation (IR) and chemotherapy. To investigate the mechanisms contributin...