STAT3: Small Molecules and Peptides

The STAT family of transcription factors, first described as key mediators of interferon signal transduction, are now recognized as signaling factors downstream of many cytokines, growth factors, and hormones. At least seven STATs exist: STAT1, 2, 3, 4, 5a, 5b, and 6. They are responsible for an array of cellular activities including regulating growth, survival, differentiation, motility, and the immune response. They are characterized structurally by the presence of the Src homology 2 (SH2) domain, and a C-terminal tyrosine phosphorylation site. Upon ligand binding, they are recruited to the activated receptor, via their SH2 domains, to receptor-associated tyrosine kinases of the Janus kinase family (JAK). Once phosphorylated by JAK, STATS are free to hetero- or homo-dimerize, and translocate to the nucleus where they bind DNA to regulate gene transcription.