INHIBITION OF E2F-4 DP-1-STIMULATED TRANSCRIPTION BY P202/

The interferon (IFN)-inducible proteins mediate activities of the inte rferons including the cell growth-regulatory activity. We have shown t hat p202, an IFN-inducible 52kDa primarily nuclear phosphoprotein whos e expression in transfected cells inhibits cell proliferation, interac ts with the retinoblastoma tumor suppressor protein (pRb) and the tran scription 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 inhibitio n of the sequence-specific DNA-binding of E2F-4 both in complex with t he 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 E 2F-4, supporting the notion that complexes containing p107/E2F-4 or p1 30/E2F-4 and p202 exist in vivo. Moreover, cotransfection of E2F-4-enc oding plasmid in AKR-2B cells overcame p202-mediated inhibition of cel l growth, raising the possibility that p202 contributes to cell growth inhibition by the interferons, at least in part, by modulating E2F-4- mediated transcription.