Regulation of the urokinase gene by the retinoblastoma protein.

Abstract

The promoter of the human urokinase plasminogen activator (uPA) gene contains a sequence identical with the retinoblastoma control element (RCE) of the murine c-fos gene, as well as several Sp1 binding sites. In a number of cell lines, the uPA promoter is activated during enforced expression of the retinoblastoma protein, pRB. Electrophoretic mobility-shift assays revealed that the RCE sequence of the uPA gene forms only one specific DNA-protein complex that does not contain pRB. The formation of the RCE-protein complex can be inhibited by 20 molar excess of the unlabeled RCE sequences and by 5 molar excess of the unlabeled E2F binding site. The RCE of the human uPA gene interacts specifically with a protein, which appears to be distinct from members of the E2F family of proteins, Sp1, ATF2, and Elf-1, which are all transcription factors shown to be regulated by pRB.