Stat5: From Breast Development to Cancer Prognosis, Prediction, and Progression

Signal transducer and activator of transcription (STAT) proteins transmit signals from extracellular polypeptides, through transmem-brane receptors, directly to target gene promoters in the nucleus re-sulting in genetic reprogramming of the target cell. There are seven STAT genes inmammals (1, 2, 3, 4, 5A, 5B, and 6)1,2 derived phyloge-netically from an ancestral gene (Stat93E) that first appeared in Dro-sophila. STAT proteins are latent transcription factors activated by tyrosine phosphorylation following recruitment to ligand-activated re-ceptor complexes. Tyrosine phosphorylation allows tail-to-tail dimeriza-tionleadingtotheiraccumulationwithinthenucleus.KnockoutofSTAT genes in mice has established their key roles in the distinct responses elicitedbyspecificpolypeptidehormoneligands,withfidelityinresponses being transmitted, in part, through specificity of binding of each STAT Src-homology 2 (SH2) domain to phosphotyrosine-containing motifs locatedwithin ligand-activated receptor complexes