The F box protein Skp2 (S-phase kinase-associated protein 2) is oncogenic, and its frequent amplification and overexpression correlate with the grade of malignancy of certain tumors. Skp2 controls p300-p53 signaling pathways in cancer cells, making it a potential molecular target for cancer therapy. This gene positively regulates the G(1)-S transition by controlling the stability of several G(1) regulators, such as the cell cycle inhibitor p27. This study provides evidence of a role for an F-box protein in oncogenesis and establishes SKP2 as a protooncogene causally involved in the pathogenesis of lymphomas.