The D-domain of Sp3 modulates its protein levels and activation of the p21CIP1/WAF1 promoter

A variety of signals result in the transcriptional induction of the p21CIP1/WAF1 promoter and both Sp1 and the related Sp3 proteins have been implicated in this induction. We have characterized the role of the C-terminal D-domains of both Sp1 and Sp3 proteins in the activation of this promoter in response to butyrate treatment of Hep G2 cells. We have defined a negative regulatory domain present in the C-terminus of Sp3. This domain decreases Sp3 protein levels, and this property can be transferred to Sp1. Changes in Sp3 protein levels may bring about growth arrest through the induction of inhibitors of the cell cycle such as p21CIP1/WAF1.