STATProteine

STATProteine, commonly called STAT proteins, are a family of transcription factors that transmit signals from cytokine and growth factor receptors at the cell surface to the nucleus, where they regulate gene expression. Activation begins when receptors recruit and activate the JAK kinases, leading to phosphorylation of specific tyrosine residues on STATProteine. Phosphorylated STATProteine dimerize, accumulate in the nucleus, and bind to DNA at gamma-activated sites (GAS) to regulate target genes. Dephosphorylation and negative regulators return STATProteine to an inactive state.

STATProteine share a modular architecture that includes an N-terminal domain for protein interactions, a central DNA-binding domain, an SH2 phosphotyrosine-binding domain, and a C-terminal transcriptional activation domain. This architecture supports rapid signal amplification and selective gene regulation. In humans, seven STAT genes exist: STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, and STAT6, with multiple splice isoforms.

STAT signaling governs immune responses, hematopoiesis, development, cell growth, and apoptosis. Each STAT member has tissue-specific and context-dependent roles; for example, STAT1 mediates interferon responses, while STAT3 and STAT5 are central to many cytokine pathways.

Dysregulation of STAT signaling is linked to disease, notably cancer, where constitutive STAT3 or STAT5 activity promotes survival and proliferation, and chronic STAT signaling contributes to autoimmunity and inflammatory disorders. Therapeutic strategies include JAK inhibitors and, in development, direct STAT antagonists.

The STAT family was identified in the 1990s, with the name reflecting its dual role as a signal transducer and a transcriptional activator. STATProteine are studied using phosphorylation assays, reporter assays with GAS elements, and chromatin-immunoprecipitation techniques.