STAT3 is required for the gp130-mediated full activation of the c-myc gene

The signal transducers and activators of transcription (STAT) family member s have been implicated in regulating the growth, differentiation and death of normal and transformed cells in response to either extracellular stimuli , including cytokines and growth factors, or intracellular tyrosine kinases , c-myc expression is coordinately regulated by multiple signals in these d iverse cellular responses. We show that STAT3 mostly mediates the rapid act ivation of the c-myc gene upon stimulation of the interleukin (IL)-6 recept or or gp130, a signal transducing subunit of the receptor complexes for the IL-6 cytokine family. STAT3 does so most likely by binding to cis-regulato ry region(s) of the c-myc gene. We show that STAT3 binds to a region overla pping with the E2F site in the c-myc promoter and this site is critical for the c-myc gene promoter-driven transcriptional activation by IL-6 or gp130 signals. This is the first identification of the linkage between a member of the STAT family and the c-myc gene activation, and also explains how the IL-G family of cytokines is capable of inducing the expression of the c-my c gene.