The Stat1 transcription factor plays a pivotal role in both, the antiviral and antigrowth actions of interferons. Stat1 acquires the ability to bind DNA by becoming phosphorylated on Tyr(701). However, to effectively stimulate gene transcription, it must also be phosphorylated on Ser(727). We show that engagement of T cell antigen receptor (TCR)/CD3 complex in either Jurkat cells or peripheral ...

BACKGROUND We have developed multiple stable cell lines containing subgenomic HCV RNA that are resistant to treatment with interferon alpha (IFN-α. Characterization of these IFN-α resistant replicon cells showed defects in the phosphorylation and nuclear translocation of STAT1 and STAT2 proteins due to a defective Jak-STAT pathway. METHODOLOGY/PRINCIPAL FINDINGS In this study, we have develop...

SUMO-1 conjugation selectively modulates STAT1-mediated gene responses Running title: Sumoylation modulates STAT1 responses Daniela Ungureanu1, Sari Vanhatupa1, Juha Grönholm1, Jorma J. Palvimo2 and Olli Silvennoinen1,3 1From Institute of Medical Technology, University of Tampere, Tampere, Finland; 3Department of Clinical Microbiology, Tampere University Hospital, Tampere, Finland; 2Department ...

PURPOSE Signal transducer and activator of transcription (STAT) proteins are important regulators of physiological stimuli in lymphocytes. Biological therapies directed at lymphocytic malignancies such as chronic lymphocytic leukemia (CLL) may be mediated by these transcription factors. One such approach, CD154 (CD40-ligand) gene therapy, involves expressing CD154 on malignant B cells from CLL ...

The aim of the study was to establish a rapid and reliable method for screening CSF1R (Colony Stimulating factor 1 Receptor) signaling pathway inhibitors. Plasmid containing human CSF1R gene was constructed and transfected into U2OS cells stably expressing GFP-STAT1 (green fluorescent protein-signal transducers and activators of transcription) fusion protein. A cell line stably expressing both ...

To elucidate the function of the transcriptional coregulator PRMT1 (protein arginine methyltranferase 1) in interferon (IFN) signaling, we investigated the expression of STAT1 (signal transducer and activator of transcription) target genes in PRMT1-depleted cells. We show here that PRMT1 represses a subset of IFNgamma-inducible STAT1 target genes in a methyltransferase-dependent manner. These g...

T cell large granular lymphocyte leukemia (T-LGLL) is a rare incurable disease that is characterized by defective apoptosis of cytotoxic CD8+ T cells. Chronic activation of the Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) pathway is a hallmark of T-LGLL. One manifestation is the constitutive phosphorylation of tyrosine 701 of STAT1 (p-STAT1). T-LGLL patients also exh...

A variety of cytokines and growth factors act through an induction of gene expression mediated by a family of latent transcription factors called STAT (signal transducers and activators of transcription) proteins. Ligand-induced tyrosine phosphorylation of the STATs promotes their homodimer and heterodimer formation and subsequent nuclear translocation. We demonstrate here that STAT protein het...

The transcription factor signal transducer and activator of transcription-1 (STAT1) is a linchpin of immunity. In the presence of the inflammatory cytokine interferon-γ (IFN-γ), STAT1 becomes phosphorylated, dimerizes, and translocates to the nucleus, where it activates transcription of genes needed for resistance to pathogens. However, STAT1 can promote the transcription of different subsets o...

AIMS Recent evidence suggests that the zonula occludens protein 2 (ZO-2) might have additional cellular functions, beyond regulation of paracellular permeability of epithelial and endothelial cells. Deregulation of ZO-2 in response to ischaemia, hypertensive stress, and vascular injury implies its involvement in cardiovascular disorders, most likely via regulating the functional behaviour of va...