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Description

Signal transducer and activator of transcription 3 (UniProt P40763, also known as Acute-phase response factor, DNA-binding protein APRF) is encoded by the STAT3 (also known as ADMIO, APRF, HIES) gene (Gene ID 6774) in human. STAT proteins (1, 2, 3, 4, 5A, 5B, 6) constitute a family of proteins that mediate cytokine and growth factor receptors-initiated signaling events. Stat3 is activated upon phosphorylation on Y705 by Jak or receptor tyrosine kinases, leading to Stat3 homodimerization, nuclear translocation, and target genes transcription. Constitutively tyrosine-phosphorylated Stat3 is implicated in the initiation and progression of many types of cancers, while Stat3 gene knockout in mice is lethal at the early embryonic stage. Two major alternatively spliced Stat3 isoforms exist, the C-terminal end 55-amino acid sequence (a.a. 716-770) in the canonical alpha isoform (UniProt P40763-1) is truncated and replaced with a 7-amino acid sequence in the 722-amino acid beta isoform (UniProt P40763-3). Tyrosine-phosphorylated Stat3beta homodimers are more stable and less susceptible to dephosphorylation, bind DNA more avidly and exhibit markedly prolonged nuclear retention than pStat3alpha homodimers.