STAT3

Article By:

Altura, Rachel A. Department of Pediatrics, Division of Hematology-Oncology, Brown University, Providence, Rhode Island.

Last reviewed:2012

DOI:https://doi.org/10.1036/1097-8542.YB120293

Signal transducer and activator of transcription 3 (STAT3) is a latent cytosolic transcription factor that signals directly from cell surface receptors to the nucleus, coupling the activation of these receptors to gene activation. Originally discovered as an acute-phase response factor that is activated after stimulation by interleukin-6 (IL-6), STAT3 was subsequently shown to participate in signaling by polypeptide growth factors and oncoproteins, linking its activation to cancer. STAT3 is encoded by an evolutionarily conserved gene and is one of a family of seven mammalian proteins (STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, and STAT6) that vary in size between 750 and 850 amino acids and share a 20–50% sequence identity. The major structural features of all STAT proteins include an N-terminal STAT dimerization domain, a coiled-coil domain involved in protein–protein interactions, a central DNA-binding domain, an Src homology (SH2) domain, a conserved tyrosine residue at position 705 (Tyr⁷⁰⁵), and a C-terminal transcriptional activation domain. Upon activation of cell surface receptors, monomeric STAT3 proteins bind to phosphorylated receptors, forming homodimers through their SH2 domains. STAT3 homodimer proteins can then translocate to the nucleus and bind DNA within promoter target sites that share a 9-base-pair (bp) consensus sequence, TTCCGGGAA. Precise regulation of STAT3 activation is critical; if STAT3 is deregulated, aberrant STAT3 signaling may contribute to malignant transformation by promoting cell-cycle progression and/or cell survival.

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