Complex roles of Stat1 in regulating gene expression

Abstract

Stat1 is a fascinating and complex protein with multiple, yet contrasting transcriptional functions. Upon activation, it drives the expression of many genes but also suppresses the transcription of others. These opposing characteristics also apply to its role in facilitating crosstalk between signal transduction pathways, as it participates in both synergistic activation and inhibition of gene expression. Stat1 is a functional transcription factor even in the absence of inducer-mediated activation, participating in the constitutive expression of some genes. This review summarizes the well studied involvement of Stat1 in IFN-dependent and growth factor-dependent signaling and then describes the roles of Stat1 in positive, negative and constitutive regulation of gene expression as well as its participation in crosstalk between signal transduction pathways. Oncogene (2000).

STAT-1 Mediates the Stimulatory Effect of IL-10 on CD14 Expression in Human Monocytic Cells

“…We provide evidence that IL-10-induced CD14 expression is mediated not through STAT-3, but through STAT-1 activation in monocytic cells. STAT-1 plays a critical role in IFN-␥-mediated biological effects such as antiproliferative responses, immune surveillance, and tumor suppression (50). The role of STAT-1 in biological responses has been studied by using STAT-1 Ϫ/Ϫ mice.…”

The Effects of Aerosolized STAT1 Antisense Oligodeoxynucleotides on Rat Pulmonary Fibrosis

“…Hence, reduction of TGF-, PDGF in lung tissues and TNF- in BALF is possibly seen as a result of the reduction of the infiltration of inflammatory cells and as a result of the decreased release by these inflammatory cells. It is also possibly seen as a result of the down-regulation of the STAT1 signaling pathway, which has been shown to be involved in cytokine effects on immunity and inflammation (9)(10)(11)(12). Accordingly, the decreased inflammatory mediators, in turn, decreased infiltration of inflammatory cells.…”

“…The first discovered STAT protein was STAT1, which correlated with immunity and inflammation. Several studies showed that STAT1 correlated with the occurrence and development of inflammatory and immune diseases (9)(10)(11)(12).…”

Aerosolized STAT1 Antisense Oligodeoxynucleotides Decrease the Concentrations of Inflammatory Mediators in Bronchoalveolar Lavage Fluid in Bleomycin-Induced Rat Pulmonary Fibrosis

“…In contrast, in many diseases, the STAT proteins are persistently activated. Many studies supported that abnormal STAT activation was involved in many diseases such as tumors, inflammatory diseases and so on (7,8).…”

“…The first discovered STAT protein was STAT1, which correlated with the occurrence and development of inflammatory and immune diseases (7)(8)(9). In previous study, we found that there was abnormal STAT1 activation in AMs of rats with bleomycin (BLM)-induced IPF based on nuclear transportation of STAT1, which led to upregulation of STAT1-dependent immune response gene intercellular adhesion molecule (ICAM-1) expression.…”