Oncogenic STRAP functions as a novel negative regulator of E-cadherin and p21 Cip1 by modulating the transcription factor Sp1

However, the functional mechanism of regulation of E-cadherin and p21 Cip1 by STRAP is unknown. Here, we have employed STRAP knock out and knockdown cell models (mouse embryonic fibroblast, human cancer cell lines) to show how STRAP downregulates E-cadherin and p21 Cip1 by abrogating the binding of Sp1 to its consensus binding sites.

Moreover, ChIP assays suggest that STRAP recruits HDAC1 to Sp1 binding sites in p21 Cip1 promoter. Interestingly, loss of STRAP can stabilize Sp1 by repressing its ubiquitination in G1 phase, resulting in an enhanced expression of p21 Cip1 by >4.5-fold and cell cycle arrest. Using Bioinformatics and Microarray analyses, we have observed that 87% mouse genes downregulated by STRAP have conserved Sp1 binding sites.