Binding of an Interferon-inducible Protein (p202) to the Retinoblastoma Protein

Many of the antimicrobial, immunomodulatory, and cell growth regulatory activities of the interferons are mediated by interferon-inducible proteins. One family of such murine proteins is encoded by six or more adjacent and structurally related genes (gene 200 cluster). Two homologous human genes have also been reported. p202, encoded by the Ifi202 gene in the gene 200 cluster, is a 52-kDa nuclear phosphoprotein. Constitutive overexpression of p202 in transfected cells is growth-inhibitory. We report here that p202 binds the cell growth regulatory retinoblastoma protein (pRb) in vitro and in vivo. The binding is due to direct interaction between the two proteins. p202 has two nonoverlapping segments for binding pRb, and pRb has two nonoverlapping segments (one of them including the pocket region) for binding p202. The hypophosphorylated form of pRb binds to p202, p202 is the first interferon-inducible protein found to bind pRb.