A critical role of Sp1 transcription factor in regulating gene expression in response to insulin and other hormones.

Specificity protein 1 (Sp1) belongs to a family of ubiquitously expressed, C(2)H(2)-type zinc finger-containing DNA binding proteins that activate or repress transcription of many genes in response to physiological and pathological stimuli. There is emerging evidence to indicate that in addition to functioning as 'housekeeping' transcription factors, members of Sp family may be key mediators of gene expression induced by insulin and other hormones. The founding member of the family, Sp1, by virtue of its multi-domain organization, potential for posttranslational modifications and interactions with numerous transcription factors, represents an ideal mediator of nuclear signaling in response to hormones. Insulin regulates the sub-cellular localization, stability and trans-activation potential of Sp1 by dynamically modulating its post-translational modification by O-linked beta-N-acetylglucosamine (O-GlcNAc) or phosphate residues. We briefly review the recent literature demonstrating that an involvement of Sp-family of transcription factors in the regulation of differential gene expression in response to hormones is more common than previously appreciated and may represent a key regulatory mechanism.