What is STAT1 mutation?
In the more severe disorder immunodeficiency 31B, the STAT1 gene mutations impair both the IFNG pathway and the IFNA/B pathway, resulting in susceptibility to both viral infections such as herpes simplex and viral encephalitis, and mycobacterial infections such as tuberculosis.
What is immunology STAT1?
STAT1 is the primary transcription factor activated by interferons so it plays a major role in normal immune responses, particularly to viral, mycobacterial and fungal pathogens.
Where is STAT1 located?
Pre-formed complexes of Stat1 with Stat2 or Stat3 have been observed in unstimulated HeLa cells (Stancato et al., 1996). Furthermore, Stat1 has also been found in the nuclei of unstimulated cells (Schindler et al., 1992). These observations are related to how Stat1 can function as a constitutive transcription factor.
What is STAT1 GOF?
STAT1 gain-of-function (GOF) is a primary immunodeficiency typically characterized by chronic mucocutaneous candidiasis (CMC), recurrent respiratory infections, and autoimmunity.
What is STAT1 and STAT2?
STAT1 and STAT2 proteins are key mediators of type I and type III interferon (IFN) signaling, and are essential components of the cellular antiviral response and adaptive immunity. They associate with IFN regulatory factor 9 (IRF9) to form a heterotrimeric transcription factor complex known as ISGF3.
What is STAT 1 gain of function?
What controls STAT1 expression?
In normal human cells treated with interferons (IFNs), the concentration of tyrosine-phosphorylated STAT1 (YP-STAT1), which drives the expression of a large number of genes, increases quickly but then decreases over a period of several hours.
What is STAT1 gain function?
What is chronic mucocutaneous candidiasis?
Chronic mucocutaneous candidiasis (CMC) refers to a heterogeneous group of disorders characterized by recurrent or persistent superficial infections of the skin, mucous membranes, and nails with Candida organisms, usually Candida albicans.
What is the function of STAT?
STAT proteins are latent cytoplasmic transcription factors activated by various extracellular signaling proteins. On activation, STAT proteins can up-regulate the transcription of various target genes and result in uncontrolled cellular proliferation, anti-apoptotic responses, and angiogenesis.
Does STAT Dimerize?
Unphosphorylated STATs can dimerize in an antiparallel conformation via extended interfaces of the globular N-domains, whereas STAT activation triggers a parallel dimer conformation with mutual phosphortyrosine:SH2 domain interactions, resulting in DNA-binding and nuclear retention.
What do ISGs do?
Function. ISGs have a wide range of functions used to combat infection at all stages of a pathogen’s lifestyle. For a viral infection, examples include: prohibiting entry of the virus into uninfected cells, stopping viral replication, and preventing the virus from leaving an infected cell.
What is the function of the STAT1 gene?
The STAT1 gene provides instructions for making a protein that is involved in multiple immune system functions, including the body’s defense against a fungus called Candida. When the immune system recognizes Candida, it generates cells called Th17 cells.
What happens to STAT1 after JAK-STAT signaling?
Termination of JAK-STAT Signaling. Activated STAT1 is not retained in the nucleus more than 1 h in normal cells. A nuclear phospho-tyrosyl phosphatase TC-PTP has been shown to dephosphorylate STAT1. STAT1 is exported back to the cytoplasm and this terminates STAT1-stimulated gene expression.
How is STAT1 related to the IFN family?
Within the STAT family, STAT1 is pivotal in mediating transcriptional responses to cytokines of the interferon (IFN) family, as well as interleukin-27 (IL-27). This is achieved by the formation of transcription complexes, known as interferon-stimulated gene factor 3 (ISGF3) and gamma-activating factor (GAF).
Are there any overexpression models for STAT1 Gof?
While over 100 mutations have been implicated in STAT1 GOF, genotype–phenotype correlation remains limited, and current overexpression models may be of limited use in gene expression studies. We generated heterozygous mutants in diploid HAP1 cells using CRISPR/Cas9 base-editing, targeting the endogenous STAT1 gene.