Stat

Acronym for "Signal Transducer and Activator of Transcription". Group of 7 known (see table) transcription factors that can be induced by interleukins. STAT proteins are involved in the immune system, growth and proliferation of cells via the JAK-STAT signalling pathway. STAT proteins can interact with a large number of signaling proteins to affect various signaling pathways.

STAT proteins have six functional domains (Yang C et al. 2020):

• N-terminal interaction domain - critical for dimerization of inactive STATs and nuclear translocation;
• helical coiled coil domain - association with regulatory factors.
• Central DNA binding domain - binding to the enhancer region of IFN-γ-activated sequence (GAS) family genes.
• Linker domain - assisting in the DNA binding process.
• Src homology 2 domain (SH2 domain) - critical for specific binding to cytokine receptor after tyrosine phosphorylation
• C-terminal transactivation domain - triggers the transcription process

Seven STAT proteins are known in humans. Mutations in STAT genes are responsible for several inherited diseases:

Janus tyrosine kinases (JAKs) and signal transducers and activators of transcription (STATs) are among the most important proteins that play key roles in cell development, proliferation, differentiation and survival. JAKs are a family of proteins belonging to a category of intracellular non-receptor tyrosine kinases. In mammals, the JAK family contains four members: JAK1, JAK2, JAK3 and TYK2.

STAT family consists of seven members STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, STAT6 which mainly act as transcription factors.

Various cytokines are involved in the activation of STAT proteins such as IL-6 and interferons. After dimer formation, STATs translocate to the nucleus and activate transcription at their target sites. The STAT signaling pathway is very fast; within minutes after cytokine stimulation, activated STATs are detectable in the nucleus.

Mutations in STAT genes are responsible for several hereditary diseases:

• Mutations of the STAT3 gene have been detected in hyper-IgE syndrome (R50.9).
• A mutation of the STAT-4 gene has been detected in a Finnish population with familial classical Kaposi's sarcoma (C46.-).
• A mutation of the STAT-5 gene was found in Laron syndrome type 2.

1. Aavikko M et al (2014) Whole-Genome Sequencing Identifies STAT4 as a Putative Susceptibility Gene in Classic Kaposi Sarcoma. J Infect Dis 211:1842-1851
2. Alcántara-Montiel JC et al (2016) Functional characterization of two new STAT3 mutations associated with hyper-IgE syndrome in a Mexican cohort. Clin Genet 89:217-221