Interaction between Sp1 and cell cycle regulatory proteins is important intransactivation of a differentiation-related gene

The stratified squamous epithelium is a model system in which to define mol ecular mechanisms underlying the switch from proliferation to differentiati on. This can be achieved through the functional dissection of keratin gene promoters, Having previously established the importance of keratin 4 in mai ntaining the differentiated phenotype in corneal epithelial cells, we inves tigated the role of Sp1-mediated transactivation of the keratin 4 promoter given the role of Sp1 in differentiation and fell cycle progression. Sp1 tr ansactivation of the keratin 4 promoter was diminished in cyclin D1-overexp ressing cells, which may be mediated through a newly described direct inter action between Sp1 and cyclin D1 and opposed by a complex between Sp1 and p RB.