Inhibition of E2F-4/DP-1-stimulated transcription by p202

Abstract

The interferon (IFN)-inducible proteins mediate activities of the interferons including the cell growth-regulatory activity. We have shown that p202, an IFN-inducible 52kDa primarily nuclear phosphoprotein whose expression in transfected cells inhibits cell proliferation, interacts with the retinoblastoma tumor suppressor protein (pRb) and the transcription factor E2F (E2F-1/ DP-1) in vitro and in vivo. p202 was shown to inhibit E2F-1/DP-1-stimulated transcription of a reporter gene and of endogenous genes. Here we report that expression of p202 inhibited E2F-4/DP-1-stimulated transcription of a reporter gene in transfected cells. Furthermore, this inhibition was associated with the inhibition of the sequence-specific DNA-binding of E2F-4 both in complex with the pocket proteins p107 or p130 and in its 'free' form in vitro. p202 bound to p107 and p130 in vitro and in vivo and also associated with E2F-4, supporting the notion that complexes containing p107/E2F-4 or p130/ E2F-4 and p202 exist in vivo. Moreover, cotransfection of E2F-4-encoding plasmid in AKR-2B cells overcame p202-mediated inhibition of cell growth, raising the possibility that p202 contributes to cell growth inhibition by the interferons, at least in part, by modulating E2F-4-mediated transcription.