Sp1 binds elements regulated by rb and regulates ctp:phosphocholine cytidylyltransferase expression

CLAUDIA ELENA BANCHIO; VANCE DE

Rosario

Congreso; SAIB; 2006

The retinoblastoma (Rb) protein is implicated in transcriptional regulation of at least five cellular genes. Co-transfection of Rb and truncated promoter constructs has defined a discrete element (retinoblastoma control element; RCE) within the promoters of each of these genes as being necessary for Rb-mediated transcriptional control. In the present report we demonstrate that two RCE elements identified within the CTP:phosphocholine citydylyltransferase alpha (CTa) proximal promoter region are essential to promote transcription. Mutations that abolish each of the RCE elements abruptly decreased CTa-transcription. Co-transfection of Rb and truncated promoter constructs demonstrated that Rb regulates CTa-expression by different mechanisms depending on the phase of the cell cycle. The regulatory effect caused by Rb on CTa expression required both the Sp1 and the RCE elements. Maximum expression was reached when both Rb and Sp1 were over-expressed and RCE elements are required for Rb to associate with the DNA. This is the first report demonstrating not only that surrounding Sp1-binding sites alter regulation mediated by Rb, but also the expression of a gene involved in PC biosynthesis shares a common regulatory pathway with genes responsible for cell growth and differentiation.