Retinoblastoma gene (Rb) is a paradigm of tumor suppressor gene. Inactivation of Rb plays a critical role in the development of human malignancies. Previous studies from our lab showed that MDM2, an oncogene frequently found amplified and overexpressed in a variety of human tumors and cancers, specifically binds to Rb C-pocket and promotes Rb protein degradation. The central acidic domain of MDM2 is essential for Rb interaction and, in particular, the 11 peptide segment (254-264, named MP1) is sufficient for Rb interaction. We therefore hypothesized that MP1 can block the interaction between Rb and MDM2, leading to accumulation of Rb protein, and Rb-mediated cell growth arrest. In this study, we generated a lentivirus expressing MP1 fusion protein (RFP-MP1) and studied its effects on the proliferation of cultured human myeloma cell line U2-OS and human lung adenocarcinoma H1299 cells by upregulating Rb protein level. The expressing of MP1 in U2-OS and H1299 results in an accumulation of Rb protein levels leading to cell proliferation inhibition. In addition, flow cytometry assay showed that MP1 can induce cell cycle G1 arrest. Moreover, expression of MP1 can inhibit E2F activity. Taken together, these results suggest that MP1 is a novel bio-active peptide which may be useful in cancer therapy.
