Deathproof: New Insights on the Role of Skp2 in Tumorigenesis

The F box protein Skp2 is frequently overexpressed in human tumors and is capable of transforming cultured cells in vitro. It has been assumed, quite reasonably, that this oncogenic property of Skp2 is directly related to its role, as part of an SCF ubiquitin ligase complex, in the ubiquitin-mediated proteolysis of negative cell cycle regulatory proteins, notably p27Kip1. However, building on earlier results indicating that silencing of Skp2 promotes apoptosis in some tumor-derived cell lines, Kitagawa and coworkers in the February 1 issue of Molecular Cell have elucidated an alternative mechanism for promotion of tumorigenesis by Skp2, specifically the suppression of p53-mediated apoptosis.