Negative regulation of Sp1 trans-activation is correlated with the binding of cellular proteins to the amino terminus of the Sp1 trans-activation domain.

Sp1 is a well characterized and ubiquitously expressed transcription factor that regulates the constitutive and induced expression of a variety of mammalian genes. It is unclear whether Sp1 activity is regulated in vivo; the mechanism by which Sp1 interacts with the basal transcription complex has not been firmly established. We report the identification of a ubiquitously expressed and evolutionarily conserved nuclear protein, p74, that specifically binds Sp1 in vivo and in vitro. p74 interacts with several portions of the Sp1 trans-activation domain in vitro, and we correlate the binding of p74 to the amino-terminal serine/threonine-rich subdomain of Sp1 with the inhibition of Sp1-mediated transcription in vivo.