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Coiled-coil domain of Signal Transducer and Activator of Transcription 4 (STAT4) This family consists of the coiled-coil (alpha) domain of the STAT4 proteins (Signal Transducer and Activator of Transcription 4, or Signal Transduction And Transcription 4). STAT4 expression is restricted to spermatozoa, myeloid cells, and T lymphocytes, making it distinct from other STATs. It acts as the major signaling transducing STATs in response to interleukin-12 (IL-12) by inducing interferon-gamma (IFNgamma), and is a central mediator in generating inflammation during protective immune responses and immune-mediated diseases. STAT4 is a critical regulator of Th1 differentiation and inflammatory disease. It is essential for the differentiation and function of many immune cells, including natural killer cells, dendritic cells, mast cells and T helper cells. STAT4-mediated signaling promotes the production of autoimmune-associated components, which are implicated in the pathogenesis of autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis and psoriasis, making STAT4 a promising therapeutic target for autoimmune diseases. Variations in STAT4 gene are linked to the development of systemic lupus erythematosus (SLE) in humans. STAT4 activation is detected in chronic liver diseases; polymorphism in STAT4 gene has been shown to be associated with the antiviral response in primary biliary cirrhosis (PBC), HCV-associated liver fibrosis, hepatocellular carcinoma (HCC), chronic hepatitis C and in drug-induced liver injury (DILI). STAT4 may inhibit HCC development by modulating HCC cell proliferation. Studies show that increased expression of STAT4 is positively correlated with the depth of invasion in colorectal cancer (CRC) patients, and the growth and invasion of CRC cells are repressed by inhibition of STAT4 expression, making STAT4 a promising therapeutic target for the treatment of CRC. |
Jiyao W et al.(2023). "The conserved domain database in 2023.",