The IL-6-type family of cytokines, which includes IL-6 as well as a number of similar cytokines and growth factors, plays a significant role in regulating gene activation, proliferation and differentiation. Transcription factors of the Stat family are known to be involved in this signal transduction pathway, undergoing phosphorylation, dimerization and translocation to the nucleus upon activation. PIAS 1, for protein inhibitor of activated Stat1 (also designated Gu/RNA helicase II binding protein), binds specifically to Stat1, blocking Stat1 DNA-binding activity and inhibiting Stat1-mediated gene activation. PIAS 1 also binds to the Gu/RNA helicase II enzyme, leading to the proteolytic cleavage of Gu/RH-II. PIAS 3 similarly binds specifically to Stat3, blocking Stat3 DNA-binding activity and inhibiting Stat3-mediated gene activation.